Audio Journal of Oncology Podcast

Chemo-Free Regimen with Neoadjuvant CDK 4/6 Inhibition plus Endocrine Therapy Benefits Patients with High-Risk ER+ HER2- Early Breast Cancer An interview with: Paul H Cottu MD PhD, Medical Oncologist and Associate Professor, Institute Curie, Paris, France BERLIN, Germany—Patients with high-risk, hormone receptor positive, HER2 negative early breast cancers, who would typically be candidates for chemotherapy, had good clinical responses, high biological responses and good rates of surgery in a clinical trial using a chemotherapy-free neoadjuvant regimen consisting of letrozole hormone therapy plus abemaciclib CDK 4/6 inhibition. Medical Oncologist Paul Cottu MD PhD from the Institute Curie in Paris, France, reported findings from RIBOLARIS trial at the 2025 Annual Congress of the European Society for Medical Oncology held in Berlin. At his poster during the conference he talked about the study findings with Audio Journal of Oncology reporter Peter Goodwin: AUDIO JOURNAL OF ONCOLOGY Paul H Cottu MD PhD IN: “[GOODWIN] I am at the European …..  OUT:  …I’m Peter Goodwin 7:56secs ESMO ABTRACT 296O: “Risk of recurrence (ROR) after neoadjuvant ribociclib plus ET in clinically high-risk ER+/HER2− BC: Preliminary analysis of the SOLTI-RIBOLARIS trial” Speaker: Paul H. Cottu (Paris, France) Authors: Paul H. Cottu (Paris, France) Aleix Prat (Barcelona, Spain) Tomás Pascual (Barcelona, Spain) Huilin Hu (East Hanover, United States of America) Estelle Roux (Basel, Switzerland, NJ) Francisco Javier Salvador Bofill (Seville, Spain) Joana M. Ribeiro (Villejuif, France) Isabel Blancas López-Barajas (Granada, Spain) Thomas Bachelot (Lyon, France) Jerome Lemonnier (Paris, France) Juan M. Ferrero-Cafiero (Barcelona, Spain) Pablo Tolosa Ortega (Madrid, Spain, Valencia) Antonio Mulero-Sánchez (Barcelona, Spain) Thayane Antoniolli Crestani (Brussels, Belgium) Roisin M. Connolly (Cork, Ireland, MD) Cynthia X. Ma (St. Louis, United States of America) Antonio C. Wolff (Baltimore, United States of America, MD) Guillermo Villacampa (Barcelona, Spain) Thibault De La Motte Rouge (Rennes, France) Joaquín Gavilá-Gregori (Valencia, Spain) Background The CDK4/6 inhibitors (CDK46/i) are approved for early-stage HR+/HER2− breast cancer (BC). The randomized neoadjuvant NeoPAL and CORALLEEN trials provided proof of concept that CDK4/6i in combination with endocrine therapy (ET) have similar activity to multi-agent chemotherapy in pts with luminal B-PAM50 based- BC subtype. The PAM50-derived ROR score was identified as an endpoint of interest after neoadjuvant CDK4/6i-ET. The RIBOLARIS trial was designed to evaluate whether pts with ROR-low disease following neoadjuvant ribociclib (RIB) and ET can safely omit adjuvant chemotherapy. Methods RIBOLARIS is an open-label, single-arm, multicenter trial in pts with primary operable stage II, grade 2/3, Ki67 ≥20%, HR+/HER2− BC who are candidates for adjuvant chemotherapy. The study evaluates safety and long-term efficacy of a non-chemo regimen (RIB-ET) in pts with tumors showing a ROR-low score after 6 neoadjuvant cycles of RIB-ET (600 mg/day 3 weeks ON/1 week OFF + ET: letrozol 2.5 mg/day) followed by surgery (within 10 days). Pts with ROR-med/high tumors will receive chemotherapy-based treatment followed by RIB-ET. This preplanned Interim Analysis analyzed safety and efficacy after 686 surgeries. We expected at least 40% of the pts to achieve a ROR-low score after neoadjuvant RIB-ET. Results Among the enrolled pts, baseline characteristics included: median age 57 (38-84), postmenopausal status 62%, tumor stage IIA 60%, node-negative 60%, and histological grade 2 74%. At data cut-off, 686 out of 1100 surgeries (62.4%) were performed. Interestingly, we observed that 361 pts (52.6%) achieved a ROR-low score (Mean 11.3, 95% CI 10.5-12.2), while 325 pts (47.4%) had a med/high ROR score (Mean 36.9, 95% CI 34.2-39.5). The most common grade 3-4 severity TEAEs were neutropenia (grade 3: 46.3%; grade 4: 3.5%) and transaminases increased (grade 3: 10.4%; grade 4: 1.5%). Conclusions These preliminary results from the RIBOLARIS trial confirm and extend the findings from CORALLEEN and NeoPAL trials, demonstrating that a subset of pts with early-stage HR+/HER2− BC achieve ROR-low disease after neoadjuvant RIB-ET and may be candidate to spare chemotherapy. There was no new safety signal. Clinical trial identification NCT05296746.

An interview with Li Zhang MD, Medical Oncologist and Full Professor, Sun Yat-sen University Cancer Center, Guangzhou, China BERLIN, Germany—A doubling of progression-free survival, and highly statistically significant benefit for overall survival, has been achieved in patients with epidermal growth factor- (EGFR-) mutated non-small cell lung cancers that had become refractory to EGFR tyrosine kinase inhibitor therapy in a study in which treatment with the antibody drug conjugate (ADC) sacituzumab tirumotecan was compared with standard platinum-based chemotherapy. At the 2025 Annual Congress of the European Society for Medical Oncology (ESMO) Professor Li Zhang MD, a medical oncologist and full professor at Sun Yat-sen University Cancer Center in Guangzhou, China, reported findings from the randomized, multi-center phase III OptiTROP-Lung04 study at a late-breaking session.  After his talk he discussed the findings with Audio Journal of Oncology reporter, Peter Goodwin: AUDIO JOURNAL OF ONCLOGY: Li Zhang MD IN: “[GOODWIN] I’m here at ……OUT:  …..I’m Peter Goodwin  8:42 secs ESMO ABSTRACT LBA5: Sacituzumab tirumotecan (sac-TMT) vs platinum-based chemotherapy in EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC) following progression on EGFR-TKIs: results from the randomized, multi-center phase III OptiTROP-Lung04 study Speaker: Li Zhang (Guangzhou, China) Authors: Li Zhang (Guangzhou, China) Wen Feng Fang (Guangzhou, China) Lin Wu (Changsha, China) Xiangjiao Meng (Jinan, China) Yu Yao (Xi’an, Shaanxi Province, China) Wei Zuo (Nanchang, China) Wenxiu Yao (Chengdu, China) Yanyan Xie (Nanning, China) Yu Zhang (Mianyang, China) Jiuwei Cui (Changchun, China) Yongchang Zhang (Changsha, China) Xingya Li (Zhengzhou, China) Wu Zhuang (Fuzhou, China) Jian Fang (Beijing, China) Qiming Wang (Zhengzhou, China) Wei Jiang (Nanning, China) Kai Li (Tianjin, China) Yina Diao (Chengdu, China) Junyou Ge (CHENGDU, China) Yunpeng Yang (Guangzhou, China) Background Sac-TMT is a TROP2 ADC developed with a novel linker to conjugate the payload, a belotecan-derivative topoisomerase I inhibitor. Sac-TMT demonstrated significant survival benefits over docetaxel in EGFRm NSCLC after failure of EGFR-TKI and platinum-based chemotherapy (Fang et al., BMJ 2025). Here, we first report the final PFS analysis and preplanned interim OS analysis results from the phase 3 OptiTROP-Lung04 study (NCT05870319). Methods Patients (pts) were randomized (1:1) to receive sac-TMT monotherapy (5 mg/kg Q2W) or chemotherapy (pemetrexed 500 mg/m2 + carboplatin AUC 5 or cisplatin 75 mg/m2 Q3W for 4 cycles followed by maintenance of pemetrexed). The primary endpoint was PFS assessed by blinded independent review committee (BIRC) with OS as a key secondary endpoint tested hierarchically. Results A total of 376 pts (median age 59.5 yrs; 39.6% male; 79.3% ECOG PS 1; 94.7% prior 3rd-generation EGFR TKI) were randomized to the sac-TMT (n=188) or chemotherapy (n=188) groups. At a median follow-up of 18.9 mo, 21.3% of pts (sac-TMT) vs 1.6% (chemotherapy) remained on treatment. Sac-TMT demonstrated highly statistically significant and clinically meaningful improvements in PFS and OS compared to chemotherapy (Table). Grade ≥ 3 TRAEs occurred in 49.5% and 52.2%, and TRSAEs in 7.4% and 17.0% of pts in sac-TMT and chemotherapy arms, respectively. No drug-related interstitial lung disease/pneumonitis occurred in either arm. Sac-TMT (n=188)      Chemotherapy (n=188) Median PFS (BIRC), mo (95% CI)  8.3 (6.7 – 9.9)  4.3 (4.2 – 5.5) HR (95% CI)  0.49 (0.39 – 0.62) P-value          <0.0001 12-mo PFS rate, %, (95% CI)           32.3 (25.5 – 39.2)        7.9 (4.4 – 12.8) Median OS, mo (95% CI)    NR (21.5 – NE)          17.4 (15.7 – 20.4) HR (95% CI)  0.60 (0.44 – 0.82) P-value          0.0006 Adjusted median OS*, mo (95% CI)          NR (21.5 – NE)          17.2 (15.4 – 18.9) HR (95% CI)  0.56 (0.41 – 0.77) P-value          0.0002 ORR (BIRC), % (95% CI)     60.6 (53.3, 67.7)         43.1 (35.9, 50.5) Median DOR (BIRC), mo (95% CI)            8.3 (6.2 – 10.0)            4.2 (3.0 – 4.4) Data cutoff: Jul 06, 2025. P-value was presented as one-sided. *censored at the date of initiation of subsequent anti-tumor ADC drug therapy. Conclusions Sac-TMT is the first TROP2 ADC to significantly improve PFS and OS over platinum-based chemotherapy, with manageable safety in EGFR-TKI resistant NSCLC, positioning it as a potential new standard of care for this population. Clinical trial identification NCT05870319. Legal entity responsible for the study Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.

An interview with: https://www.audiomedica.com/wp-content/2025/11/251019-Erwei-Song-ESMO-2025-PRODUCTION-MASTER.mp3, Director of Health Science Center, President, Sun Yat-sen Memorial Hospital, Guangzhou (SYSU), Guangzhou, China. BERLIN, Germany—The open-label HORIZON-Breast01 phase-three study has reported early data showing that, for previously treated patients with advanced or metastatic breast cancer, progression-free survival improved from a median of 8.3 months with pyrotinib plus capecitabine standard of care to 30.6 months among patients in the experimental arm who received monotherapy with the new antibody drug conjugate (ADC) trastuzumab resetecan. Furthermore, the ADC had a favorable safety profile with low occurrence of interstitial lung disease (ILD). Findings were reported at the 2025 Annual Congress of the European Society for Medical Oncology by Erwei Song MD PhD, Director of the Health Science Center, President, Sun Yat-sen Memorial Hospital, Guangzhou (SYSU), in Guangzhou, China. After his talk at the conference, Professor Song discussed the findings with Audio Journal of Oncology reporter Peter Goodwin: Audio Journal of Oncology: Erwei Song MD PhD IN: “[GOODWIN] I am at ……  OUT:  …….of Oncology, I’m Peter Goodwin. 7:42secs ESMO ABSTRACT LBA19: “SHR-A1811 versus pyrotinib plus capecitabine in human epidermal growth factor receptor 2-positive (HER2+) advanced/metastatic breast cancer (BC): A multicenter, open-label, randomized, phase III study (HORIZON-Breast01)” Speaker: Erwei Song (Guangzhou, China) Authors: Erwei Song (Guangzhou, China) Herui Yao (Guangzhou, China) Huiping Li (Beijing, China) Yongmei Yin (Nanjing, China) Qing Yuan Zhang (Harbin, China) Shusen Wang (Guangzhou, China) Quchang Ouyang (Changsha, China) Tao Sun (Shenyang, Liaoning, China) Xiaojia Wang (Hangzhou, China) Weimin Xie (Nanning, China) Biyun Wang (Shanghai, China) Wei Li (Changchun, China) Min Yan (Zhengzhou, China) Cuizhi Geng (Shijiazhuang, China) Yuan Peng (Beijing, China) Yaping Yang (Guangzhou, China) Fangli Dong (Shanghai, China) Ying Zhang (Shanghai, China) Lin Cheng (Shanghai, China) Xiaoyu Zhu (Shanghai, China) Background SHR-A1811, a HER2-targeted antibody-drug conjugate, proved substantial single agent antitumor activity in heavily pretreated solid tumors as shown in a global phase 1 trial (J Clin Oncol. 2024). Here, we first report the interim analysis of SHR-A1811 versus pyrotinib plus capecitabine in HER2+ advanced/metastatic BC from the pivotal phase 3 HORIZON-Breast01 study. Methods Taxane- and trastuzumab-pretreated patients (pts) with HER2+ advanced/metastatic BC were randomized (1:1) to receive intravenous SHR-A1811 or oral pyrotinib plus capecitabine. The primary endpoint was PFS by blinded independent central review (BICR). Results As of Jun 30, 2025, 287 pts were randomized (SHR-A1811, n=142; pyrotinib plus capecitabine, n=145; IHC 3+: 76.1% vs. 71.7%; HR+: 47.9% vs. 47.6%; median lines of prior systemic treatments: 1 vs.1; prior pertuzumab: 71.8% vs. 72.4%), with median follow-up of 15.9 months (95% CI 14.6–17.1) for SHR-A1811, and 15.3 months (95% CI 14.3–16.6) for pyrotinib plus capecitabine. The PFS by BICR was significantly improved in the SHR-A1811 group than in the pyrotinib plus capecitabine group (30.6 months vs. 8.3 months; HR 0.22 [95% CI 0.15–0.34]; p<0.0001; table). Although the median OS was not yet reached, SHR-A1811 showed a clear OS benefit trend. Median treatment duration was 19.5 months (95% CI 17.3–NR) with SHR-A1811, 7.1 months (95% CI 5.6–9.2) with pyrotinib, and 7.5 months (95% CI 5.7–9.6) with capecitabine. Similar rates of TRAEs were observed. Interstitial lung disease (ILD) occurred only in 4 pts (2.8%) receiving SHR-A1811 (grade 1/2: 3 [2.1%]; grade 3: 1 [0.7%]). Conclusions SHR-A1811 exhibited significant PFS benefit and strong trend in OS benefit versus pyrotinib plus capecitabine in the second-line therapy in HER2+ advanced/metastatic BC, with favorable safety profile of low ILD occurrence. Clinical trial identification NCT05424835. Legal entity responsible for the study Jiangsu Hengrui Pharmaceuticals Co., Ltd. Funding Jiangsu Hengrui Pharmaceuticals Co., Ltd. Disclosure Dong, Y. Zhang, L. Cheng, X. Zhu: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Pharmaceuticals Co., Ltd.

An interview with: Andrew Clamp MD, PhD, Consultant Medical Oncologist, Christie Hospital, Manchester, UK BERLIN, Germany—An important therapeutic gain in terms of overall- and progression-free survival has been achieved merely by changing the chemotherapy dose schedule given to patients with high-risk stage three or four epithelial ovarian cancer. This was reported from the ICON8B: GCIG phase-three randomised trial by Andrew Clamp MD PhD of the Christie Hospital in Manchester, England, at the 2025 Annual Congress of the European Society for Medical Oncology. Dr. Clamp discussed the findings with our reporter, Peter Goodwin. Audio Journal of Oncology interview: Andrew Clamp MD, PhD IN: “[GOODWIN] I’m at the European ….. OUT: ….Journal of Oncology, I’m Peter Goodwin”  7:21secs https://www.annalsofoncology.org/article/S0923-7534(25)02624-9/pdf ESMO ABSTRACT: 1064O – ICON8B: GCIG phase III randomised trial comparing first-line weekly dose-dense chemotherapy + bevacizumab to three-weekly chemotherapy + bevacizumab in high-risk stage III-IV epithelial ovarian cancer (EOC): Final overall survival (OS) analysis Speaker: Andrew R. Clamp (Manchester, United Kingdom) Authors: Andrew R. Clamp (Manchester, United Kingdom) Iain McNeish (London, United Kingdom) Domenico Radice (London, United Kingdom) Rosemary Lord (Liverpool, United Kingdom) Agnieszka Michael (Guildford, United Kingdom, Surrey) Audrey Cook (Cheltenham, United Kingdom) Roshan Agarwal (Northampton, United Kingdom, Northamptonshire) Axel Walther (Bristol, United Kingdom) Sarah P. Blagden (Oxford, United Kingdom) Dearbhaile O’Donnell (Dublin, Ireland) James D. Brenton (Cambridge, United Kingdom) Sudha Sundar (Birmingham, United Kingdom) Cristiana Sessa (Bellinzona, Switzerland) Laura R. Murphy (London, United Kingdom) Francesca Schiavone (London, United Kingdom) Aleksandra Gentry-Maharaj (London, United Kingdom) Richard S. Kaplan (London, United Kingdom) Mahesh K. Parmar (London, United Kingdom, London) Jonathan A. Ledermann (London, United Kingdom) ESMO Abstract Background In ICON8B the use of dose-dense weekly paclitaxel (ddwT) with 3-weekly (q3w) carboplatin (C) and bevacizumab (BEV) as first-line treatment improved median progression-free survival (PFS) by 5.5 months (m) compared to standard q3w paclitaxel (T) dosing with C+BEV (22.2m vs 16.7m; Hazard Ratio (HR) 0.75, 95% CI 0.62-0.90 p=0.002). We now report the final OS analysis conducted at trial closure. Methods Eligible participants (pts) with high-risk stage III (residual disease >1cm diameter after immediate primary surgery (IPS) or requirement for primary chemotherapy) or stage IV EOC were randomised 1:1:1 to Arm B1 (standard- q3w C AUC5/6+q3w T 175mg/m2+ q3w BEV 7.5mg/kg); Arm B2- (q3w C AUC5/6+ddwT 80mg/m2); Arm B3- (q3w C AUC5/6+ddwT 80mg/m2+ q3w BEV 7.5mg/kg). Up to six cycles chemotherapy and 18 BEV cycles were administered. Arm B2 recruitment discontinued after ICON8 saw no evidence of PFS improvement with q3wCddwT vs q3wCT. OS was a key secondary outcome and pts were followed for survival endpoints until trial closure on 18th Dec 2024 at end of academic funding. Results From 07/2015 to 03/2020 579 pts were randomised to arms B1 + B3. Median age was 64 years; 91% had High Grade Serous Carcinoma; 93% Stage IIIc/IV; 84% primary chemotherapy with planned delayed primary surgery, 14% IPS, 2% inoperable; 50.2% cases sequenced for germline BRCA1/2 mutations. After a median follow-up of 72.0m, 411 deaths were reported (197 in B3; 214 in B1). Median OS was 49.8m (95% CI 43·7-54.5m) in B3 and 39.6m (95% CI 34·7-45·0m) in B1 (HR 0·79, 95% CI 0·65-0·95, p=0·010). In pts receiving primary chemotherapy, median OS was 47.3m (95% CI 42.0-52.6m) in B3 and 37.1m (95% CI 32.3-42.1m) in B1. Conclusions In pts with high-risk stage III-IV EOC, the use of ddwT in combination with q3w C + BEV as first-line systemic therapy improves median OS by 10.2m compared to q3w T dosing. ddwT with q3wC+BEV should now be considered a standard-of-care first-line treatment option in this group. Further research is required to determine whether efficacy of this regimen is impacted by tumour homologous recombination deficiency and intrinsic chemosensitivity. Clinical trial identification ISRCTN10356387. Legal entity responsible for the study University College London. Funding Cancer Research UK and Medical Research Council.

An interview with Nima Nabavizadeh MD, Associate Professor of Radiation Medicine, Oregon Health & Science University (OHSU), Portland, USA, Chief Medical Officer, Cancer Early Detection Research Center, Portland, Oregon. https://www.audiomedica.com/wp-content/2025/11/251107-Nima-Nabavizadeh-MD-ESMO-2024-PRODUCTION-MASTER.mp3 BERLIN, Germany—A pan-cancer early detection test, that identifies “methylation fingerprints” for a wide range of cancers, has been shown to find more cancers sooner than conventional screening according to research reported to the European Society for Medical Oncology (ESMO) 2025 Annual Congress. Nima Nabavizadeh MD, Associate Professor of Radiation Medicine at the Oregon Health & Science University (OHSU) in Portland, USA, who is also Chief Medical Officer of the Cancer Early Detection Research Center in Portland, Oregon gave a report on the safety and performance of the test at the ESMO congress.  Afterwards he spoke with our reporter, Peter Goodwin: Audio Journal of Oncology: Nima Nabavizadeh MD IN:  “[GOODWIN]I am at the ESMO meeting …. OUT:  ……of oncology.  I’m Peter Goodwin”  9:55sec ESMO ABSTRACT LBA64: Safety and performance of a multi-cancer early detection (MCED) test in an intended-use population: Initial results from the registrational PATHFINDER II study https://assets.grail.com/wp-content/uploads/2025/10/ESMO-2025_PF2-Initial-Results_Presentation_FINAL-CLEAN-10.16.2025.pdf Speaker: Nima Nabavizadeh (Portland, United States of America) Authors: Nima Nabavizadeh (Portland, United States of America) Charles McDonnell III (Sacramento, United States of America) Dax Kurbegov (Nashville, United States of America) Marc Matrana (New Orleans, United States of America) Shirish Gadgeel (Detroit, United States of America) Raymond H. Kim (Toronto, Canada) Gretchen Stipec (Fountain Valley, United States of America) Kevin Oeffinger (Durham, United States of America) Michael J. Demeure (Newport Beach, United States of America) Roland Matthews (Atlanta, United States of America) Rebecca Kaltman (Fairfax, United States of America) Tamar Toronjadze (Flushing, United States of America) Cora N. Sternberg (New York, United States of America) Jennifer Tran (Washington, United States of America) Natalia Colocci (Mountain View, United States of America) Leonardo Forero (Amarillo, United States of America) Margarita Lopatin (Menlo Park, United States of America) Margaret McCusker (Menlo Park, United States of America) Karthik Giridhar (Rochester, United States of America) Background The MCED test (Galleri®) detects cancer signals from cell-free DNA in blood and predicts cancer signal origin (CSO) to guide diagnostic (dx) evaluation. PATHFINDER 2 (PF2; NCT05155605) assesses its safety and performance in a large, diverse intended-use population. Methods PF2 is a prospective, multicenter, interventional study that enrolled participants (ppts) aged ≥50y with no clinical suspicion of cancer and no cancer diagnosis/treatment in the past 3y. Primary objectives were safety and performance of the MCED test. Ppts with an MCED cancer signal detected (positive) result underwent dx evaluation based on predicted CSO(s). This prespecified initial analysis included ppts with 12m follow-up (fu) as of Dec 31, 2024. A 3y fu is planned. Results 35,878 ppts were enrolled. Of 23,161 performance analyzable ppts with 12m fu, 216 (0.93%) had a positive MCED test. Specificity was 99.6% (95% CI 99.5-99.7%); positive predictive value (PPV) was 61.6% (54.9-67.8%). First CSO prediction accuracy was 91.7% (85.8-95.3%). Episode sensitivity during 12m fu was 73.7% (65.6-80.4%) in a prespecified subgroup of 12 cancers responsible for ⅔ of US cancer deaths and 40.4% (35.3-45.8%) in all cancers. Of 329 ppts with cancer, 200 had screen-detected cancers: 133 by MCED testing (114 new primaries; 19 recurrent), 20 by USPSTF A/B and 47 by USPSTF C recommended screening tests. Of 133 MCED-detected cancers (MCED cancer detection rate: 0.57%), 75.2% do not have common screening options. Of 114 MCED-detected new primaries, 53.5% were stage I-II; 69.3% were stage I-III. Median time to dx resolution was 46d (IQR 42-59). Of 25,114 safety analyzable ppts, 159 (0.6%) had a protocol-directed invasive procedure. Invasive procedures were ∼2x more common for ppts dx with cancer vs not dx after a positive MCED test. Conclusions MCED testing increased the number of screen-detected cancers nearly 7-fold when added to USPSTF A/B recommended screening (3-fold when added to USPSTF A/B/C). Most MCED-detected new primaries were early stage. With PPV exceeding that of standard of care screening tests and a favorable safety profile, these initial PF2 results support the MCED test’s use for population-scale screening. Clinical trial identification NCT05155605. Editorial acknowledgement Medical writing support for the development of this abstract, under the direction of the authors, was provided by Jennifer Hepker, PhD, and Alexandra L. Thomas, PhD, of Citrus Health Group (Chicago, IL, USA), and was funded by GRAIL, Inc.

An interview with: Xiuning Le MD PhD, Medical Oncologist, Department of Thoracic Medicine, UT MD Anderson Cancer Center, Houston TX BERLIN, Germany—Mutations in the HER2 molecule can be found in a few per cent of non-small cell lung cancers, and these can now be targeted by the new drug sevabertinib that can bring benefit to patients who have the mutation. That’s according to findings from the SOHO-01 study reported at the 2025 Annual Congress of the European Society of Clinical Oncology. After her talk at the congress, first author Xiuning Le MD PhD, who is a medical oncologist in the Department of Thoracic Medicine, at the University of Texas MD Anderson Cancer Center, in Houston, talked about the new data with Audio Journal of Oncology reporter Peter Goodwin: Audio Journal of Oncology; Xiuning Le MD PhD IN:   “[GOODWIN] I am at the European Society for Medical ….OUT: ……. For the Audio Journal of Oncology, I’m Peter Goodwin”  10: 18secs 2025 ESMO Berlin ABSTRACT LBA75: Sevabertinib (BAY 2927088) in advanced HER2-mutant non-small cell lung cancer (NSCLC): Results from the SOHO-01 study Speaker: Xiuning Le (Houston, United States of America) Authors: Xiuning Le (Houston, United States of America) Tae Min Kim (Seoul, Republic of Korea) Xiaorong Dong (Wuhan, China) Herbert Ho Fung Loong (Hong Kong, Hong Kong SAR, China) Nicolas Girard (Paris, France) Shun Lu (Shanghai, China) Hye Ryun Kim (Seoul, Republic of Korea) Boon-Cher Goh (Singapore, Singapore) Arsela Prelaj (Milan, Italy) Yong Fang (Hangzhou, China) Lin Wu (Changsha, China) Yuki Shinno (Tokyo, Japan) Gennaro Daniele (Rome, Italy) Tsung-Ying Yang (Taichung City, Taiwan) Gerrina Ruiter (Amsterdam, Netherlands) Jun Zhao (Beijing, China) Jan Christoph Brase (Basel, Switzerland) Rui Li (Whippany, United States of America) Paolo Grassi (Milan, Italy) Lin Li (Beijing, China) Background Sevabertinib is a potent, reversible, oral HER2 tyrosine kinase inhibitor with FDA Breakthrough Therapy Designation and Priority Review for pretreated patients (pts) with advanced HER2-mutant NSCLC. We report updated efficacy and safety in pretreated and treatment-naïve pts with HER2-mutant NSCLC in the open-label, multicenter Phase I/II SOHO-01 study. Methods Pts with HER2-mutant NSCLC were treated with sevabertinib 20 mg twice daily in 3 cohorts: Cohort D, previous systemic therapy but naïve to HER2 ex20ins-targeted therapy; Cohort E, previous HER2-targeted antibody-drug conjugates; Cohort F, naïve to systemic anti-cancer therapy for advanced disease. The primary endpoint was objective response rate (ORR) by RECIST v1.1 and blinded independent central review. Secondary endpoints were duration of response (DoR) and progression-free survival (PFS). Results At the data cut-off (June 27, 2025), 209 pts with HER2-mutant NSCLC were treated: 81 (D), 55 (E), and 73 (F). ORR (95% CI) was 64% (53, 75; D), 38% (25, 52; E), and 71% (59, 81; F). Median (95% CI) DoR was 9.2 (6.3, 13.5; D), 8.5 (5.6, 16.4; E), and 11.0 (8.1, not evaluable; F) months; 12-month DoR rates (95% CI) were 42% (27, 57; D) and 29% (5, 53; E). Median PFS (95% CI) was 8.3 (6.9, 12.3; D) and 5.5 (4.3, 8.3; E) months, and not reached (F). In Cohort D, pts with baseline brain metastases had a similar ORR to those without (61% vs 65%). Among pts with HER2 tyrosine kinase domain (TKD) mutations, those with Y772_A775dupYVMA had a higher ORR (78% vs 57%) and median PFS (12.2 vs 7.0 months) than those with other HER2 TKD mutations. Overall, grade ≥3 treatment-related adverse events (TRAEs) were reported in 31% of pts. Diarrhea was the most commonly reported TRAE, mostly grade 1/2 (grade 3: 14%). TRAEs led to treatment discontinuation in 3% of pts; none due to diarrhea. There were no reports of interstitial lung disease or pneumonitis. Conclusions Sevabertinib showed rapid and durable responses with a manageable safety profile in pretreated and treatment-naïve pts with advanced HER2-mutant NSCLC. These data support sevabertinib as a potential practice-changing, new targeted therapy for pts with HER2-mutant NSCLC. Clinical trial identification: NCT05099172, March 28, 2025. Editorial acknowledgement: Alice Xue, MSc, Erica Sedgwick, MSc, and Rachel Fairbanks, BA, of Caudex, IPG Health Medical Communications, provided medical writing and editorial assistance in the development of this abstract, funded by Bayer AG. Legal entity responsible for the study: Bayer AG. New England Journal of Medicine https://www.nejm.org/doi/full/10.1056/NEJMoa2511065    

An interview with: Christof Vulsteke MD PhD, Medical Oncologist, Head of the Integrated Cancer Center Ghent, Belgium BERLIN, Germany—Patients with muscle invasive bladder who were ineligible for cisplatin chemotherapy gained large, clinically meaningful and statistically significant benefits from treatment with the antibody drug conjugate enfortumab vedotin combined with pembrolizumab checkpoint inhibition in the phase three KEYNOTE-905 study. At the 2025 Annual Congress of the European Society for Medical Oncology (ESMO) Medical Oncologist Christof Vulsteke, Head of the Integrated Cancer Centre in Ghent, Belgium, reported marked improvements of event-free and overall survival among patients treated with the new combination, in comparison with those receiving standard radical cystectomy plus pelvic lymph node dissection.  After his talk in Berlin he gave more details to Audio Journal of Oncology reporter Peter Goodwin: Audio Journal of Oncology: Christof Vulsteke MD PhD; IN: “[GOODWIN] I am at the ESMO meeting in Berlin ……OUT:  …Goodwin for the Audio Journal of Oncology, Goodbye  7:12 secs ESMO 2025 ABSTRACT No. LBA2 “Perioperative (periop) enfortumab vedotin (EV) plus pembrolizumab (pembro) in participants (pts) with muscle-invasive bladder cancer (MIBC) who are cisplatin-ineligible: The phase III KEYNOTE-905 study” Speaker: Christof Vulsteke (Gent, Belgium) Authors: Christof Vulsteke (Gent, Belgium) Hristos Kaimakliotis (Indianapolis, United States of America) Pongwut Danchaivijitr (Bangkok, Thailand) Maksym Y. Sabadash (Lviv, Ukraine) Alejo Rodriguez-Vida (Barcelona, Spain) Zhentao Zhang (Fort Wayne, United States of America) Vagiz Atduev (Nizhny Novgorod, Russian Federation) Yunus Emre Goger (Konya, Türkiye) Steffen Rausch (Tuebingen, Germany) Seok Ho Kang (Seoul, Republic of Korea) Yohann Loriot (Villejuif, France) Jens Bedke (Stuttgart, Germany) Matthew D. Galsky (New York, United States of America) Peter H. O’Donnell (Chicago, United States of America) Michael Mihm (Chicago, United States of America) Changting Meng (Groton, United States of America) David Huang (Rahway, United States of America) Chethan Ramamurthy (North Wales, United States of America) Blanca Homet Moreno (Madrid, Spain) Anders Ullén (Stockholm, Sweden) Background Radical cystectomy + pelvic lymph node dissection (RC + PLND) is the standard treatment for pts with MIBC who are cisplatin-ineligible. Periop therapy may improve outcomes in these pts. Methods The phase 3 KEYNOTE-905/EV-303 study (NCT03924895) evaluated efficacy and safety of periop EV + pembro and RC + PLND vs RC + PLND in adult pts with MIBC (T2-T4aN0M0 or T1-T4aN1M0) who were cisplatin-ineligible or declined cisplatin. Pts were randomized 1:1 to EV + pembro (3 cycles EV 1.25 mg/kg on d1 and d8 + pembro 200 mg on d1 Q3W, followed by RC + PLND, then 6 cycles EV + 14 cycles pembro) vs control (RC + PLND only). Study therapy continued until progression, unacceptable adverse events (AEs), withdrawal of consent, or completion of planned treatment. The primary endpoint was event-free survival (EFS) by blinded independent central review. Secondary endpoints were overall survival (OS; key), pathological complete response (pCR) rate (key), and safety. Results 170 pts were randomized to EV + pembro and 174 pts to control. >80% of pts were cisplatin-ineligible per Galsky criteria. As of Jun 6, 2025, median follow-up time was 25.6 mo (range, 11.8–53.7). 149 pts (87.6%) in the EV + pembro arm and 156 (89.7%) in the control underwent surgery. EV + pembro significantly improved EFS (median not reached [NR] vs 15.7 mo; HR 0.40; 95% CI 0.28–0.57; P<.001), OS (NR vs 41.7 mo; HR 0.50; 95% CI 0.33–0.74; P<.001), and pCR rate (57.1% vs 8.6%; estimated difference 48.3%; 95% CI 39.5–56.5; P<.001) vs control. Treatment-emergent AEs occurred in 100% (gr ≥3, 71.3%) of pts in the EV + pembro arm and 64.8% (gr ≥3, 45.9%) in the control. Most frequent gr ≥3 AE of special interest (based on distinct prespecified lists for each drug) was severe skin reactions (grouped term; 11.4%) for pembro, and skin reactions (grouped term; 10.8%) for EV. Conclusions Adding periop EV + pembro to surgery significantly and meaningfully improved EFS, OS, and pCR rate in pts with MIBC who were predominantly cisplatin-ineligible. The safety profile of EV + pembro was manageable and consistent with prior reports. This is the first perioperakthrough regimen to improve outcomes vs RC + PLND in this setting and may be a new standard of care. Clinical trial identification: NCT03924895.

An interview with: Xichun Hu MD PhD, Professor, Director, Department of Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China BERLIN, Germany—In a head-to-head comparison of two antibody drug conjugates used to treat unresectable or metastatic breast cancer, patients treated with trastuzumab botidotin lived more than twice as long before disease progression than those in the control arm receiving trastuzumab emtansine (T-DM1).  This finding was announced by Chinese researchers at the 2025 Annual Congress of the European Society of Medical Oncology. Lead author Xichun Hu MD PhD, Professor, Director, Department of Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China talked about the findings of his groups phase three randomized controlled study with Audio Journal of Oncology reporter Peter Goodwin: AUDIO JOURNAL OF ONCOLOGY: Xichun Hu MD PhD IN:  “[GOODWIN] Peter Goodwin at ESMO ..OUT:  ..of Oncology, I’m Peter Goodwin  8:30 sec ESMO ABSTRACT LBA24 “Trastuzumab botidotin vs trastuzumab emtansine (T-DM1) in HER2-positive unresectable or metastatic breast cancer: Results from a randomized phase III study” Speaker: Xichun Hu (Shanghai, China) Authors: Xichun Hu (Shanghai, China) Jian Zhang (Shanghai, China) Quchang Ouyang (Changsha, China) Qingyuan Zhang (Harbin, China) Huihui Li (Jinan, China) Xu Wang (Tianjin, China) Ying Wang (Guangzhou, China) Yongmei Yin (Nanjing, China) Shusen Wang (Guangzhou, China) Yuanting Gu (Zhengzhou, Algeria) Tao Sun (Shenyang, China) Jingfen Wang (Linyi, China) Xinhong Wu (Wuhan, China) Fanfan Li (Hefei, China) Xi Chen (Fuzhou, China) Man Li (Dalian, China) Jin Yang (Xi’an, Shaanxi Province, China) Hua Yang (Baoding, China) Xiaoping Jin (Chengdu, China) Junyou Ge (CHENGDU, China) Lecture Time ASTRACT Background Trastuzumab botidotin (A166) is a HER2-directed ADC developed using a stable, protease-cleavable valine-citrulline linker conjugated to the anti-microtubule agent Duo-5. In a phase 1 study, A166 showed promising activity in heavily pretreated patients (pts) with HER2+ breast cancer (BC). Here, we first report the results from a phase 3 study (NCT06968585).   Methods Pts with HER2+ unresectable or metastatic BC who had received at least one prior anti-HER2 therapy were randomized (1:1) to receive A166 (4.8 mg/kg Q3W) or T-DM1 (3.6 mg/kg Q3W) until disease progression or unacceptable toxicity. The primary endpoint was PFS by BICR per RECIST v1.1.   Results A total of 365 pts were randomized (median age 55 years; 73.4% with visceral metastases; 53.4% received ≥2 prior anti-HER2 therapies; 55.9% had prior pyrotinib). As of 26 April 2025, median follow-up was 14.9 mo. Median PFS was significantly longer in A166 than in T-DM1 (11.1 mo vs 4.4 mo; HR 0.39 [95% CI 0.30-0.51], p<0.0001). PFS benefit with A166 was consistently observed regardless of prior lines of anti-HER2 therapy (HR 0.36 for 1 prior line; HR 0.39 for ≥2 prior lines). ORR by BICR was 76.9% vs 53.0%, and mDOR was 12.2 mo vs 5.7 mo. Although OS data were immature, a trend toward benefit was observed in A166 (HR 0.62; 95% CI, 0.38-1.03). Grade ≥3 TEAEs occurred in 69.8% of pts in A166 and 63.7% in T-DM1. The most common grade ≥3 TEAEs (≥5%) were corneal disorder, dry eye, and vision blurred in A166, and platelet count decreased, neutrophil count decreased, hypokalemia, and GGT increased in T-DM1. Among A166-treated pts who experienced any-grade ocular AEs, instrumental activities of daily living (ADL) limitations occurred in 37 (20.3%) pts, and self-care ADL limitations in 13 (7.1%) pts; these resolved in 32 (86.5%) and 12 (92.3%) pts, respectively. TEAEs led to discontinuation in 1.1% of pts in A166 and 3.8% in T-DM1. No TEAE led to death in A166, compared with 1.1% in T-DM1. Conclusions A166 demonstrated statistically significant and clinically meaningful improvement in PFS compared with T-DM1, with a manageable safety profile in pts with HER2+ unresectable or metastatic BC. These results position A166 as a potential new therapeutic option for HER2+ disease. Clinical trial identification NCT06968585. Legal entity responsible for the study Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. Funding Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. Disclosure Jin, J. Ge: Financial Interests, Institutional, Full or part-time Employment: Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. All other authors have declared no conflicts of interest. Xichun Hu MD, PhD Medical Oncology Xuhui, Shanghai, China Xi-Chun Hu, M.D., Ph. D., is currently a Professor, Director of the Department of Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China. Dr. Hu has published more than 170 papers in the journals, such as Lancet Oncology, JCO, and International Journal Cancer, and 5 book chapters. He is vice editor of the ABC (Advanced breast cancer) guideline (Chinese version) and one of the leading authors of the CBCS (Chinese Breast Cancer Society) guideline for breast cancer diagnosis and treatment which is updated biannually. Dr. Hu is an active member of the American Society of Clinical Oncology, General secretary & Member of the standing committee of CBCS (Chinese Breast Cancer Society), Vice-chair of Shanghai Breast Cancer Society, Member of the Standing Academic Committee of CSCO (Chinese Society of Clinical Oncology). Dr. Hu’s major interest is in the diagnosis and management of breast cancer, both in the clinic and in the laboratory, and in phase I trial on new anticancer agents. His laboratory interests and contributions have been in the area of serum tumor markers, epigenetic alteration and gene expression, and detection of residual disease. He and his laboratory are now concentrating on translational research on triple-negative breast cancer and angiogenesis.

An interview with: Martin Wermke MD, TU Dresden, NCT/UCC Early Clinical Trial Unit and Medical Clinic, Poliklinik I, Natural Centre for Tumor Diseases, Dresden, Germany BERLIN, Germany—The prospect of markedly better outcomes for patients with small cell lung cancer, with “encouraging initial survival outcomes”, was raised by findings from the DeLLphi-303 study, reported at the European Society for Medical Oncology (ESMO) 2025 Annual Congress. The bi-specific T-cell engager drug tarlatamab was included with initial therapy for patients with extensive stage small cell lung cancer. Martin Wermke MD, from TU Dresden, Director of the NCT/UCC Early Clinical Trial Unit and of the Medical Clinic, Poliklinik I, Natural Centre for Tumor Diseases in Dresden, Germany reported the latest study data to the ESMO congress. After his talk he gave the details to our reporter Peter Goodwin: Audio Journal of Oncology; Martin Wermke MD: ”[GOODWIN] Peter Goodwin here at the ESMO meeting   ………….of Oncology, I’m Peter Goodwin.”  6:16secs https://pubmed.ncbi.nlm.nih.gov/40934933/ ESMO ABSTRACT 2757O Tarlatamab with first-line chemoimmunotherapy for extensive stage small cell lung cancer (ES-SCLC): DeLLphi-303 study Speaker: Martin Wermke (Dresden, Germany) Authors Martin Wermke (Dresden, Germany) Sally Lau (Toronto, Canada) Mor T. Moskovitz (Petah Tikva, Israel) Ingel Demedts (Roeselare, Belgium) Kelly Paulson (Seattle, United States of America) Aurélie Swalduz (Lyon, France) Cornelius Waller (Freiburg, Germany) Luis Paz-Ares (Madrid, Spain) Makoto Nishio (Koto-ku, Japan) Michael Boyer (Camperdown, Australia, NSW) James Chih-Hsin Yang (Taipei City, Taiwan) Amanda Parkes (Thousand Oaks, United States of America) Yuyang Zhang (Thousand Oaks, United States of America) Ali Hamidi (Thousand Oaks, United States of America) Mukul Minocha (Thousand Oaks, United States of America) Pedro F. Simoes da Rocha (Barcelona, Spain) Background: Tarlatamab with anti-PD-L1 achieved notable survival outcomes with manageable safety as maintenance therapy following 1L platinum-etoposide chemotherapy and anti-PD-L1 (1L chemo-IO) for ES-SCLC. In this phase Ib study (parts 2, 4, 7), the safety and efficacy of adding tarlatamab to 1L chemo-IO was assessed. Methods: Patients (pts) had received 1 cycle of 1L chemo-IO prior to enrollment. On study, pts received 3 cycles of tarlatamab + 1L chemo-IO followed by tarlatamab + anti-PD-L1 Q3W until progression. Tarlatamab was administered 20 mg Q3W with a 1 mg step dose. Primary endpoints included dose-limiting toxicities (DLTs), treatment-emergent (TE), and treatment-related (TR) adverse events (AEs). Key secondary endpoints were objective response (OR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results: Of 96 pts enrolled, 3 (3%) had DLTs. TEAEs and TRAEs were reported in all pts. The most common TRAEs were cytokine release syndrome (CRS, 56%), anemia (54%), and dysgeusia (46%). Grade (Gr) ≥ 3 TRAEs occurred in 72 pts (75%), most commonly neutropenia/neutrophil count decreased (44%), anemia (23%), and lymphopenia/lymphocyte count decreased (11%), primarily within the first two cycles. CRS (54% Gr 1-2; 2% Gr 3-4) and ICANS and associated neurological events (5% Gr 1-2; 1% Gr 3) TRAEs were mostly low grade. Other immune-related AEs were rare (2%). From a baseline scan after 1 cycle of 1L chemo-IO, OR rate following tarlatamab addition to 1L chemo-IO was 71%, with median DOR of 11.0 months (mo) (95% CI 6.7-not estimable). Median PFS was 9.0 mo. With a median follow-up time of 11.3 mo, the Kaplan-Meier estimate of OS at 12 mo was 81% (Table). Results from further follow-up will be presented. Table: 2757O Safety and efficacy of tarlatamab + chemoimmunotherapy as 1L treatment for ES-SCLC Conclusions: The combination of tarlatamab with chemo-IO for 1L treatment of ES-SCLC demonstrated manageable safety with encouraging initial survival outcomes, supporting further investigation of this combination in the phase III DeLLphi-312 study. Clinical trial identification: NCT05361395. Editorial acknowledgement Medical writing support for the development of this abstract was provided by Sukanya Raghuraman, PhD, of Cactus Life Sciences, part of Cactus Communications, and Liz Leight, PhD, an employee of Amgen Inc., and was funded by Amgen Inc. Legal entity responsible for the study: Amgen Inc. Funding: Amgen Inc.

An interview with:  John P. Crown MD MBA, Consultant Medical Oncologist, St. Vincent’s University Hospital, Dublin, Professor of Translational Cancer Research, Dublin City University, Professor of Medicine, University College Dublin   Ireland. BERLIN, Germany—Patients with high-risk node-negative ER-positive HER2-negative early breast cancer who had the CDK 4/6 inhibitor drug ribociclib added to their non-steroidal aromatase inhibitor (AI) adjuvant therapy after surgery had significantly longer freedom from progression to invasive disease compared with patients receiving the AI alone.  This is according to five-year data from the NATALEE trial reported at the 2025 Annual Congress of the European Society for Medical Oncology. Professor John P. Crown MD MBA, Consultant Medical Oncologist, from St. Vincent’s University Hospital in Dublin gave reporter Peter Goodwin the latest details: Audio Journal of Oncology,  John P. Crown MD MBA, IN: “[GOODWIN] I am at the ESMO meeting, 2025, in Berlin ….OUT:  signing off for the Audio Journal of Oncology.” 11:24 secs 2025 ESMO: Proffered Paper Friday 14:00 Oct 17, 2025 Abstract Title: LBA14 – Adjuvant ribociclib (RIB) plus nonsteroidal aromatase inhibitor (NSAI) in patients (pts) with HR+/HER2− early breast cancer (EBC): NATALEE 5-year outcomes Speaker: John P. Crown (Dublin, Ireland) Authors: John P. Crown (Dublin, Ireland) Daniil Stroyakovskiy (Moscow, Russian Federation) Denise Yardley (Chattanooga, United States of America) Chiun-Sheng Huang (Taipei City, Taiwan) Peter A. Fasching (Erlangen, Germany) Aditya Bardia (Los Angeles, United States of America) Stephen Chia (Vancouver, Canada) Seock-Ah Im (Seoul, Republic of Korea) Miguel Martin (Madrid, Spain) Binghe Xu (Beijing, China) Carlos H. Barrios (Porto Alegre, Brazil) Michael Untch (Berlin, Germany) Rebecca Moroose (Lake Mary, United States of America) Sara A. Hurvitz (Seattle, United States of America, CA) Gabriel N. Hortobagyi (Houston, United States of America) Dennis Slamon (Los Angeles, United States of America) Frances Visco (Washington, United States of America) Gonzalo Spera (Montevideo, Uruguay) Zheng Li (East Hanover, United States of America) Sherene Loi (Melbourne, Australia, VIC) Background: The phase 3 NATALEE trial demonstrated that adjuvant RIB + NSAI led to a statistically significant invasive disease–free survival (iDFS) benefit in pts with stage II and III HR+/HER2− EBC. We present a protocol-specified 5-year efficacy analysis. Methods: Pts with HR+/HER2− EBC were randomized 1:1 to RIB (400 mg/d; 3 weeks on/1 week off for 3 y) + NSAI (letrozole 2.5 mg/d or anastrozole 1 mg/d for 5 y) or NSAI alone. Men and premenopausal women received goserelin. Pts were included if they had anatomical stage IIA (if N1 [1-3 axillary lymph nodes] or N0 with additional high-risk factors), stage IIB, or stage III disease per AJCC, 8th ed. The primary end point of iDFS and secondary efficacy end points of distant disease–free survival (DDFS), distant relapse–free survival (DRFS), and overall survival (OS) were evaluated using Kaplan-Meier methods. Statistical comparisons were made by stratified log-rank test. Results: At data cutoff (May 28, 2025), all pts were off RIB treatment, and a similar proportion had completed 5 years of NSAI treatment in both arms (RIB + NSAI, 36.5%; NSAI alone, 34.4%). With a median iDFS follow-up of 55.4 months, RIB + NSAI demonstrated persistent iDFS benefit over NSAI alone (hazard ratio [HR], 0.716; 95% CI: 0.618-0.829; nominal 1-sided P<.0001). Absolute iDFS rates were 90.8% vs 88.0% at 3 y, 88.3% vs 83.9% at 4 y, and 85.5% vs 81.0% at 5 y (absolute improvement of 2.7%, 4.4%, and 4.5%, respectively). iDFS benefit was observed across subgroups, including N0 (HR, 0.606; 95% CI: 0.372-0.986). RIB + NSAI also demonstrated continued DDFS (HR, 0.709; 95% CI: 0.608-0.827) and DRFS (HR, 0.699; 95% CI: 0.594-0.824) benefit vs NSAI alone. A positive trend for OS favoring RIB + NSAI (HR, 0.800; 95% CI: 0.637-1.003; nominal 1-sided P=.026) continues to emerge. No new safety signals were observed with a median follow-up time of approximately 2 years after RIB completion. Conclusions: In this 5-year landmark analysis with mature efficacy data, RIB + NSAI reduced the risk of invasive and distant disease recurrence compared with NSAI alone, including in pts with high-risk N0 disease. A positive trend for OS in favor of RIB + NSAI continues to emerge.

An interview with: Javier C Cortés MD PhD, Breast Cancer Medical Oncologist, IOB Madrid, Institute of Oncology, Madrid, and International Breast Cancer Centre, Barcelona, Spain BERLIN, Germany—Treatment with the antibody drug conjugate (ADC) sacituzumab govitecan (that targets the Trop-2 cancer-associated protein, delivering a cytotoxic topoisomerase inhibitor payload) has significantly improved progression-free survival in patients with newly-diagnosed metastatic triple-negative breast cancer who were not candidates for treatment with immune checkpoint inhibition and had received no prior therapy. At the European Society for Medical Oncology (ESMO) 2025 Annual Congress Javier C Cortés MD PhD from the Institute of Oncology in Madrid and the International Breast Cancer Centre in Barcelona reported data from the ASCENT-03 study showing that treatment with sacituzumab govitecan brought clinically meaningful benefits with toxicities that were found to be manageable. At the congress Cortés talked about the new findings with Peter Goodwin: Audio Journal of Oncology: Javier C Cortes MD PhD “[GOODWIN] Peter Goodwin here in Berlin …..……….Audio Journal of Oncology, I’m Peter Goodwin.   9:47secs ESMO ABSTRACT: LBA20 – “Primary results from ASCENT-03: A randomized phase III study of sacituzumab govitecan (SG) vs chemotherapy (chemo) in patients (pts) with previously untreated advanced triple-negative breast cancer (TNBC) who are unable to receive PD-(L)1 inhibitors (PD-[L]1i)” Speaker: Javier C. Cortés (Barcelona, Spain) Authors: Javier C. Cortés (Barcelona, Spain), Aditya Bardia (Los Angeles, United States of America), Kevin Punie (Antwerp, Belgium), Carlos H. Barrios (Porto Alegre, Brazil), Sara A. Hurvitz (Seattle, United States of America, CA),Andreas Schneeweiss (Heidelberg, Germany), Joohyuk Sohn (Seoul, Republic of Korea), Eriko Tokunaga (Fukuoka, Japan), Adam M. Brufsky (Pittsburgh, United States of America, PA), Yeon Hee Park (Seoul, Republic of Korea), Binghe Xu (Beijing, China), Roberto Hegg (São Paulo, Brazil), Mafalda Oliveira (Barcelona, Spain), Alessandra Fabi (Rome, Italy), Natalya Vaksman (Miami, United States of America), Theresa Valdez (Miami, United States of America), Xinrui Zhang (Miami, United States of America), Catherine Lai (Foster City, United States of America, CA), Sara M. Tolaney (Boston, United States of America, MA) Background Significant PFS benefit was observed with SG vs chemo in pretreated metastatic (m)TNBC (ASCENT) and with SG + pembrolizumab vs chemo + pembrolizumab in first-line (1L) PD-L1+ mTNBC (ASCENT-04). For pts with mTNBC who cannot receive PD-(L)1i, treatment options are limited. We report primary results from the randomized phase 3 ASCENT-03 study (NCT05382299) of 1L SG vs chemo in pts with locally advanced unresectable or mTNBC who are unable to receive a PD-(L)1i. Methods Pts had centrally confirmed PD-L1− mTNBC (defined as combined positive score [CPS] < 10) or PD-L1+ mTNBC (CPS ≥ 10) but were unable to receive PD-(L)1i due to a comorbidity or prior use in the curative setting. Randomization (1:1) to SG (10 mg/kg IV, days 1 & 8 in 21-day cycles) or chemo (paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin) was stratified by disease status and geography. The primary end point was PFS by BICR. Key secondary end points included overall survival (OS), ORR and DOR by BICR, and safety. Results 558 pts (279 in each group) with mTNBC were randomized. With a median follow-up of 13.2 mo, SG showed a significant improvement in median PFS vs chemo (9.7 vs 6.9 mo; HR, 0.62; 95% CI, 0.50-0.78; P < .0001); median DOR was 12.2 mo vs 7.2 mo (Table). OS data were immature. The most frequent grade ≥ 3 TEAEs were neutropenia (43%) and diarrhea (9%) with SG and neutropenia (41%) and anemia (16%) with chemo. Conclusions SG led to a statistically significant and clinically meaningful improvement in PFS and more durable responses vs chemo in 1L mTNBC. The safety profile of SG was manageable and consistent with its known profile; treatment discontinuation rate due to TEAEs was lower with SG vs chemo. These data support SG as a potential new standard of care for pts with previously untreated mTNBC who are unable to receive a PD-(L)1i. Table: LBA20 Clinical trial identification NCT05382299. Editorial acknowledgement Editorial assistance was provided by Peggy Robinet, PharmD, PhD, and Sonal S. Joshi, PhD, of Parexel, and funded by Gilead Sciences, Inc. Legal entity responsible for the study Gilead Sciences, Inc. Funding Gilead Sciences, Inc. PRESS RELEASE: ASCENT-03: Trodelvy® Demonstrates Highly Statistically Significant & Clinically Meaningful Improvement in Progression Free Survival in Patients With First-line Metastatic Triple-Negative Breast Cancer Who Are Not Candidates for Checkpoint Inhibitors – Second Positive Phase 3 Trial in First-line Metastatic TNBC Where Trodelvy Has Demonstrated a Clinically Meaningful Benefit Versus Standard of Care Chemotherapy – – Trodelvy Has the Potential to Be the Backbone of Treatment and the First Antibody-Drug Conjugate for All Patients Across First-line Metastatic TNBC – FOSTER CITY, Calif.–(BUSINESS WIRE)– Gilead Sciences, Inc. (Nasdaq: GILD) today announced positive topline results from the Phase 3 ASCENT-03 study of Trodelvy® (sacituzumab govitecan-hziy). The study met its primary endpoint, demonstrating a highly statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to chemotherapy in patients with first-line metastatic triple-negative breast cancer (mTNBC) who are not candidates for PD-1/PD-L1 inhibitors, meaning they are PD-L1 negative or are ineligible to receive immunotherapy. “Almost half of the patients diagnosed with metastatic triple-negative breast cancer do not receive treatment beyond first-line, demonstrating an urgent need for innovative treatment options in this early setting,” said Dr. Javier Cortes, Head of the International Breast Cancer Center in Spain and principal investigator of the ASCENT-03 study. “Traditional chemotherapy has been the standard of care for early treatment of metastatic triple-negative breast cancer, and we know that therapeutic advances in this disease area serve a critical unmet need for patients and the broader oncology community.” Together with the recently announced positive results from the ASCENT-04 study evaluating Trodelvy plus Keytruda® in patients with previously untreated PD-L1+ metastatic TNBC, Trodelvy now has the potential to be the backbone treatment for all patients across first-line mTNBC. Detailed data from the ASCENT-04 study will be shared during the American Society of Clinical Oncology (ASCO) meeting taking place May 30 – June 3, 2025. “The ASCENT-03 outcome represents the first clinically meaningful advance for this patient population in over 20 years versus chemotherapy,” said Dietmar Berger, MD, PhD, Chief Medical Officer, Gilead Sciences. “By addressing this aggressive and difficult to treat disease earlier, we can potentially improve treatment options for the high unmet need that patients with metastatic triple-negative breast cancer face.” The safety profile of Trodelvy in the ASCENT-03 study was consistent with prior studies, and no new safety signals were identified in this patient population. Overall survival (OS) is a key secondary endpoint and was not mature at the time of PFS primary analysis. No OS detriment was observed. Gilead will continue to monitor OS outcomes, with ongoing patient follow-up and further analysis planned. Detailed results from the ASCENT-03 study will be presented at a future medical meeting and discussed with regulatory authorities. The use of Trodelvy in first-line mTNBC is investigational, and the safety and efficacy of this use have not been established. Healthcare professionals have well-established experience with Trodelvy, which has shown generally consistent outcomes across both clinical trials and real-world studies in 60,000+ patients across 50+ countries over approximately five years. It is the only antibody-drug conjugate (ADC) with four positive Phase 3 trials in HER2- (IHC 0, IHC 1+ or IHC 2+/ISH–) metastatic breast cancer (mBC), and remains the only approved Trop-2-directed ADC that has demonstrated meaningful survival advantages in two different types of metastatic breast cancers: 2L mTNBC and pre-treated HR+/HER2- mBC. Trodelvy is a Category 1 preferred treatment for both currently approved indications per the National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology (NCCN Guidelinesi) and the only ADC with an ESMO Magnitude of Clinical Benefit Scale (MCBS) rating of 5 for mTNBC. Trodelvy also has an MCBS rating of 4 for women with HR+/HER2- mBC. Currently, Gilead has additional ongoing Phase 3 studies investigating Trodelvy across HER2- (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer including the ASCENT-07 pivotal trial in patients with HR+/HER2- mBC who have received endocrine therapy, and the ASCENT-05 pivotal trial in patients with early-stage TNBC (eTNBC). Trodelvy is also being evaluated in additional Phase 3 studies across a range of tumor types, including in lung and gynecologic cancers. Gilead would like to thank the patients, families, investigators and advocates who have contributed and continue to contribute to this important research. We remain committed to advancing care to address the unmet needs for the breast cancer community. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. About Triple-Negative Breast Cancer (In Patients Who Are Not Candidates for PD-1/PD-L1 inhibitors) Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer and has historically been difficult to treat, accounting for approximately 15% of all breast cancers. TNBC disproportionately impacts younger, pre-menopausal as well as Black and Hispanic women. TNBC cells do not have estroge

    An interview with: Trevor Leong  MD, Peter McCallum Cancer Centre, Radiation Oncology Department, Melbourne, Australia BARCELONA, Spain—Although pre-operative radiotherapy brought better response rates in patients resected for their gastric or GE-junction adenocarcinomas, there was no improvement in survival. This is the clear finding from a big, long-term study led by an Australian team. The multi-continent, phase-three randomized TOP GEAR trial, headquartered in Sydney Australia, definitively found no benefit for overall or progression-free survival from adding radiation before surgery. This clear finding was announced at the 2024 Annual Meeting of the European Society for Medical Oncology (ESMO), held in Barcelona, Spain First author Trevor Leong MD, from the Radiation Oncology Department of the Peter McCallum Cancer Centre in Melbourne Australia, talked about the results with  Peter Goodwin: Trevor Leong MD interview (8mins 37 secs): IN: “Resectable gastric or gastro-esophageal…. OUT:  ,,’till next time, Good-bye.” ESMO 2024, Barcelona, ABSTRACT: 03880-8/fulltext “A randomised phase three trial of perioperative chemotherapy (CT) with or without pre-operative chemoradiotherapy (CRT) for resectable gastric cancer (AGITG TOPGEAR). Final results from an intergroup trial of AGITG, TROG, EORTC and CCTG”. NEJM September 13, 2024: https://www.nejm.org/doi/full/10.1056/NEJMoa2405195 TITLE: “Preoperative Chemoradiotherapy for Resectable Gastric Cancer” From:  The Australasian Gastro-Intestinal Trials Group, National Health and Medical Research Council Clinical Trials Centre, Trans-Tasman Radiation Oncology Group, European Organisation for Research and Treatment of Cancer, and Canadian Cancer Trials Group. JOURNAL Article: N Engl. J Med.: “The addition of preoperative chemoradiotherapy to perioperative chemotherapy did not improve overall survival as compared with perioperative chemotherapy alone among patients with resectable gastric and gastroesophageal junction adenocarcinoma.” “A randomised phase three trial of perioperative chemotherapy (CT) with or without pre-operative chemoradiotherapy (CRT) for resectable gastric cancer (AGITG TOPGEAR). Final results from an intergroup trial of AGITG, TROG, EORTC and CCTG”.  Background In Western countries, the current standard of care for resectable gastric cancer is periop CT. There is much interest in preop CRT, but comparison to periop CT alone is lacking. In TOPGEAR we hypothesized that adding preop CRT to periop CT would improve pathological complete response (pCR) rates and ultimately overall survival (OS) compared to periop CT alone. Methods This international phase 3 trial randomized patients with resectable adenocarcinoma of the stomach and gastro-esophageal junction to periop CT alone, or with preop CRT. The periop CT alone group received 3 cycles of epirubicin/cisplatin/5-fluorouracil (ECF) or 4 cycles of fluorouracil/leucovorin/oxaliplatin/docetaxel (FLOT) both pre- and post-operatively. The preop CRT group received one less cycle of preop chemotherapy followed by chemoradiotherapy (45 Gy in 25 fractions radiation plus infusional 5-FU ), and then the same postop chemotherapy. The primary endpoint was overall survival, and secondary endpoints included progression free survival (PFS), pCR rates, toxicity and quality of life. Results Between September 2009 and May 2021, 574 patients were enrolled from 70 sites across 15 countries in Australasia, Europe, and Canada; 288 to periop CT group and 286 to preop CRT group. Compared to periop CT alone, patients receiving preop CRT achieved a higher pCR rate (16.7% vs 8.0%), a higher rate of major pathological response (0 – <10% residual tumor: 49.5% vs 29.3%), and greater tumor downstaging following resection. After a median follow-up of 66.7 months, there was no significant difference in OS or PFS: median OS periop CT 49.4 months vs preop CRT 46.4 months; median PFS periop CT 31.8 months vs preop CRT 31.4 months. Preop CRT was not associated with increased perioperative treatment toxicity or a higher rate of surgical complications. Conclusions Despite improving pathological outcomes, the addition of preop CRT to periop CT does not improve overall survival compared to periop CT alone in patients with resectable gastric and gastro-esophageal junction adenocarcinoma. Clinical trial identification ACTRN12609000035224. Registered 30 May 2009; NCT01924819. Legal entity responsible for the study Australasian Gastro-Intestinal Trials Group (AGITG). Funding This work was supported by grants from the National Health and Medical Research Council: 1046425 and 2000711, Canadian Institutes of Health Research (CIHR) grant no. 119445, the Canadian Cancer Society Research Institute (CCSRI) grant no. 021039, the Health Research Council of New Zealand (HRC) International Investment Opportunities Fund: Contract no. 09/624, the EORTC Cancer Research Fund, and the Cancer Australia Priority-driven Collaborative Research Scheme: Project ID: 570996. Disclosure K.M. Haustermans: Financial Interests, Personal, Other, Clinical editor Radiotherapy & Oncology: Elsevier; Financial Interests, Institutional, Funding: IBA; Financial Interests, Institutional, Research Grant: Varian, https://www.audiomedica.com/wp-content/2025/10/Trevor-Leong-ESMO-AJO-PRODUCTION-MASTER.mp3Editorial acknowledgement Editorial and medical writing support was provided in accordance with Good Publication Practice guidelines by Lewis Cawkwell, PhD, of Parexel, and was funded by AstraZeneca. Legal entity responsible for the study AstraZeneca.          

An interview with: Domenica Lorusso MD PhD, Director of the Gynaecological Oncology Unit, full Professor of Obstetrics and Gynaecology, Humanitas Hospital San Pio X, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University of the Sacred Heart, Rome, Italy. Both overall and progression-free survival were significantly improved when the anti-PD-1 agent pembrolizumab was added to standard chemoradiotherapy as initial treatment for patients with high-risk locally advanced cervical cancer. Results from the randomized, double-blind, phase III KEYNOTE-A18 study of immunotherapy, used together with standard concurrent chemoradiotherapy among 1060 patients, were reported by a multinational team of researchers led from Italy to the 2024 Annual Congress of the European Society for Medical Oncology in Barcelona. The study lead author Domenica Lorusso MD PhD, Director of the Gynaecological Oncology Unit at Humanitas Hospital San Pio X, in Milan, who is a Full Professor of Obstetrics and Gynaecology at Humanitas University, Rozzano, met up with Peter Goodwin to discuss the KEYNOTE-A18 findings. Audio Journal of Onclogy: Domenica  Lorusso MD PhD IN: “Immune checkpoint inhibition  …..OUT:  …….in Barcelona at the ESMO meeting”. Durn: 7:20 secs ESMO Abstract 7090 Lorusso, Gynaecology Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS and Catholic University of the Sacred Heart, Rome, Italy “Pembrolizumab plus chemoradiotherapy for high-risk locally advanced cervical cancer: Overall survival results from the randomized, double-blind, phase III ENGOT-cx11/ GOG-3047/KEYNOTE-A18 study” Background At the first interim analysis of the phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study (NCT04221945), pembrolizumab (pembro) + concurrent chemoradiotherapy (CCRT) showed a statistically significant and clinically meaningful improvement in PFS vs placebo (pbo) + CCRT in patients (pts) with high-risk locally advanced cervical cancer (LACC). Based on this study, the US FDA has approved pembro + CCRT for pts with FIGO 2014 Stage III-IVA cervical cancer. We present the OS results from the second interim analysis.Methods Eligible pts with newly diagnosed, previously untreated, high-risk LACC (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA regardless of lymph node status) were randomized 1:1 to 5 cycles of pembro 200 mg or pbo Q3W + CCRT, then 15 cycles of pembro 400 mg or pbo Q6W. CCRT included 5 cycles (optional 6th dose) of cisplatin 40 mg/m2 Q1W + EBRT then brachytherapy. Pts were stratified by planned EBRT type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), stage at screening (IB2-IIB vs III-IVA), and planned total radiotherapy dose (<70 Gy vs ≥70 Gy [EQ2D]). Primary endpoints are PFS per RECIST v1.1 by investigator and OS.Results 1060 pts were randomized to pembro + CCRT (n=529) or pbo + CCRT (n=531). At this analysis (January 8, 2024, data cutoff), median follow-up was 29.9 mo (range, 12.8-43.0). Pembro + CCRT showed a statistically significant improvement in OS compared with pbo + CCRT. The 36-mo OS rate was 82.6% with pembro + CCRT vs 74.8% with pbo + CCRT; median OS was NR in either group (HR=0.67 [95% CI, 0.50-0.90]; P=0.0040). The benefit of pembro + CCRT was generally consistent in all prespecified subgroups, including FIGO stages IB2-IIB (HR=0.89 [95% CI, 0.55-1.44]) and III-IVA (HR=0.57 [95% CI, 0.39-0.83]). Grade ≥3 TRAE incidence was 69.1% in the pembro + CCRT group and 61.3% in the pbo + CCRT group. Conclusions Pembro + CCRT showed a statistically significant and clinically meaningful improvement in OS vs pbo + CCRT in pts with high-risk LACC and had a manageable safety profile. These data provide further support for pembro + CCRT as a new standard of care for this population. Clinical trial identification NCT04221945; EudraCT: 2019-003152-37. Editorial acknowledgement Medical writing assistance was provided by Christine McCrary Sisk of Merck & Co., Inc., Rahway, NJ, USA. This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, Audio Journal of Oncology, October 6, 2025    

An interview with: James Larkin FRCP, PhD, Medical Oncologist, Professor, Royal Marsden Hospital, London Checkpoint inhibitor therapy for advanced melanoma has achieved sustained responses and long-term overall survival, transforming the prognosis for as many as half of all patients. 10-year survival outcomes from the phase Ill CheckMate 067 trial of nivolumab plus ipilimumab in advanced melanoma were reported at the 2024 Annual Meeting of the European Society for Medical Oncology (ESMO) held in Barcelona. Peter Goodwin, talked with study author, James Larkin FRCP PhD, Professor and Medical Oncologist at the Royal Marsden Hospital in London. Audio Journal of Oncology: James Larkin FRCP PhD: IN:  “There’s been breath-taking progress ………OUT:  join me then, Good-bye!” 14:57secs   SOURCE: Annals of Oncology: https://www.annalsofoncology.org/article/S0923-7534(24)03864-X/fulltext ESMO Abstract LBA43 Larkin, Medicine Department, The Royal Marsden Hospital, London, UK “10-y survival outcomes from the phase Ill CheckMate 067 trial of nivolumab plus ipilimumab in advanced melanoma” Abstract LBA43 Larkin, Medicine Department, The Royal Marsden Hospital, London, UK “10-y survival outcomes from the phase Ill CheckMate 067 trial of nivolumab plus ipilimumab in advanced melanoma” Background In CheckMate 067, improved survival with nivolumab plus ipilimumab (NIVO + IPI) or NIVO alone v IPI has been demonstrated in patients (pts) with advanced melanoma. We now provide the final CheckMate 067 results (minimum f/u 10 y), the longest reported in a phase 3 study of an anti–programmed death (PD)-1–based therapy for any tumor type. Methods Pts with untreated advanced melanoma (N = 945) were randomly assigned 1:1:1 and stratified by PD-ligand (L)1 status, BRAF mutation status, and metastasis stage to receive NIVO (1 mg/kg) + IPI (3 mg/kg) Q3W for 4 doses, followed by NIVO (3 mg/kg) Q2W; NIVO (3 mg/kg) Q2W + placebo; or IPI (3 mg/kg) Q3W for 4 doses + placebo until progression or unacceptable toxicity. Co-primary endpoints were OS and PFS with NIVO + IPI or NIVO v IPI; melanoma-specific survival (MSS) was an exploratory endpoint. Results After a 10-y minimum f/u, median OS was 71.9 mo with NIVO + IPI, 36.9 mo with NIVO, and 19.9 mo with IPI. OS HRs were 0.53 (95% CI, 0.44–0.65) with NIVO + IPI vIPI and 0.63 (0.52–0.76) for NIVO v IPI, and benefit was consistent across subgroups (including PD-L1 expression and BRAF mutation status). Median MSS was not reached (NR) with NIVO + IPI (> 120 mo), 49.4 mo with NIVO, and 21.9 mo with IPI. In pts who had PFS for ≥ 3 y, 10-y MSS rates were 96% with NIVO + IPI, 97% with NIVO, and 88% with IPI. Only 8 pts, 4 in the NIVO + IPI arm and 4 in the NIVO arm, progressed beyond 60-mo of f/u. For pts in the NIVO + IPI arm who discontinued treatment during induction due to a treatment-related adverse event, 10-y OS rates were the same as the ITT group (43%) and MSS rates were similar (50% v 52%).  Table: LBA43” MORE: James Larkin is a Medical Oncologist specialising in the treatment of cancers of the kidney and skin including melanoma. Professor Larkin grew up in North Cornwall before taking a first in Natural Sciences from Cambridge University. He undertook clinical training in Oxford, qualifying in 1996. His general medical training was undertaken in London and in 2001 he won a Medical Research Council Research Fellowship for a Clinician, carrying out laboratory research leading to a PhD at the Institute of Cancer Research. His specialist training was completed at The Royal Marsden, where he was appointed as a Consultant in 2008. His research is focussed on trying to understand cancer and its consequences better, as well as developing improved treatments, particularly with targeted therapies and immunotherapies. Globally, he is amongst the most highly cited researchers in both melanoma and kidney cancerThis link is external and opens in a new tab. In 2018, he was elected as a Fellow of the Academy of Medical Sciences and in 2020 as an NIHR Senior Investigator. In 2022, he was appointed to roles as Head of The Royal Marsden Skin Unit, Royal Marsden Joint Training Programme Director for Medical Oncology and Lead of the Cancer Immunotherapy Theme at The Royal Marsden / Institute of Cancer Research NIHR Biomedical Research Centre. Since 2024, he has hosted the educational podcast ‘Melanoma Matters’ with his US colleague Professor Sapna Patel, and in 2026 he will be Scientific Co-Chair of the Annual European Society of Medical Oncology meeting in Madrid. Professor Larkin serves as a medical advisor to the patient advocacy group Melanoma UK, as a trustee of Action Kidney Cancer and sits on the Medical Advisory Board of the International Kidney Cancer Coalition.      

An interview with: Jefferson DeKloe BSc, Department of Otolaryngology, Thomas Jefferson University, Philadelphia, PA CHICAGO, USA—Although the take-up of vaccination for human papilloma virus (HPV) among girls and boys in the USA has been lower than in many other industrial countries, American researchers have now shown clearly that in addition to the prevention of cervical cancer in women, men have also been protected against HPV-related cancers. At the 2024 American Society of Clinical Oncology Annual (ASCO) Meeting in Chicago a new study of HPV vaccination of girls and boys in the United States revealed a real-world reduction of oral, plus head and neck cancers in men, as well confirming the prevention of cervical cancers in women, even though uptake of the vaccine in the US had been sub-optimal. The study looked at HPV-associated cancer incidence in a retrospective cohort analysis of patients from the TriNetX Collaborative Network. At the ASACO meeting Peter Goodwin met up with the lead author of the research, Jefferson DeKloe BSc, from the Department of Otolaryngology at Thomas Jefferson University in Philadelphia USA. Audio Journal of Oncology, with: Jefferson DeKloe BSc IN:  “HPV Vaccination …..OUT: ……, I’m Peter Goodwin”.  6:00secs https://meetings.asco.org/abstracts-presentations/231759 “Effects of HPV vaccination on the development of HPV-related cancers: A retrospective analysis of a United States-based cohort.” https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.10507 Effects of HPV vaccination on the development of HPV-related cancers: A retrospective analysis of a United States-based cohort. ALSO: https://www.sciencedirect.com/science/article/pii/S1043661825002762 HPV vaccination and malignancy risks beyond cervical cancer: A retrospective global cohort study Authors: Christian Seebauer, Mohamed Faluogy, Peter Sieg , Henning Olbrich, Ralf Ludwig Department of Oral and Maxillofacial Surgery/Plastic surgery, University Medicine Lübeck, Ratzeburger Allee 160, Lübeck 23538, Germany Department of Dermatology, Allergy, and Venerology, University of Lübeck, Ratzeburger Allee 160, Lübeck 23538, Germany Department of Dermatology, Allergy, and Venerology, Institute of Experimental Dermatology, University of Lübeck, Comprehensive Center for Inflammation Medicine, University-Hospital Schleswig-Holstein, Ratzeburger Allee 160, Lübeck 23538, Germany Received 28 April 2025, Revised 5 July 2025, Accepted 6 July 2025, Available online 11 July 2025, Version of Record 14 July 2025. HPV vaccination significantly reduced hypopharyngeal and laryngeal cancer risk. Vaccination was associated with a marked decrease in leukemia incidence. No significant protection observed for rectal, anal, or oral cavity cancers. HPV vaccination halved all-cause mortality at 8- and 20-year follow-up. Data support possible HPV involvement in hematopoietic and neuronal tissues. Abstract: While HPV vaccination is well established for the prevention of cervical cancer, its broader oncological effects remain insufficiently characterized. Emerging evidence suggests potential protective effects against non-cervical malignancies; however, comprehensive long-term data are limited. We conducted a global, retrospective cohort study utilizing electronic health records from the TriNetX network. Individuals vaccinated against HPV at age 8 years or older were propensity score-matched to unvaccinated controls. Outcomes included the incidence of malignancies in the head-and-neck, gastrointestinal, anogenital, neuronal, and hematologic systems, as well as all-cause mortality, assessed over 8- and 20-year follow-up periods. Kaplan–Meier survival analysis and hazard ratios (HRs) were employed. HPV vaccination was associated with significant reductions in the risk of hypopharyngeal and laryngeal carcinomas (8-year HR: 0.19; 95 % CI: 0.057–0.631; p = 0.0025; 20-year HR: 0.227; 95 % CI: 0.067–0.764; p = 0.0092) and leukemia (8-year HR: 0.461; p = 0.0035; 20-year HR: 0.443; p = 0.0019). No significant protection was observed for rectal, anal, oral cavity, or prostate cancers. All-cause mortality was reduced by nearly half among vaccinated individuals (8-year HR: 0.543; 20-year HR: 0.536; both p < 0.0001). Beyond epithelial malignancies, HPV vaccination may confer systemic cancer protection, particularly in hematologic and potentially neuronal tissues. These findings suggest a broader biological impact of HPV vaccination than previously recognized and underscore the need for mechanistic studies investigating HPV’s oncogenic pathways. If validated, these results could prompt the expansion of vaccination strategies to encompass broader indications and wider population coverage.            

An interview with Rebecca Dent MD, Deputy Chief Executive Officer, National Cancer Centre, Singapore, ESMO 2024 Scientific Chair. ESMO Previous Highlights: Neo-Adjuvant Therapy for Triple Negative Breast Cancer, Checkpoint Inhibition, AI, Cancer Vaccines, and More ……” BARCELONA, Spain—At the last Annual Meeting of the European Society for Medical Oncology (ESMO), medical oncologist Rebecca Dent MD, Deputy Chief Executive Officer at the National Cancer Centre in Singapore, told Peter Goodwin what had, for her, been the key areas of progress in cancer medicine announced at the meeting in which significant advances had been made. Audio Journal of Oncology with Rebecca Dent MD IN: [Goodwin] “With the 2025 meeting of ESMO about to happen …. OUT:  ….in Singapore. Thanks very much.  13:13 secs https://www.esmo.org/meeting-calendar/esmo-congress-2024/programme         MORE: Professor Rebecca Dent MD MSc is a career-long clinical and translational researcher as well as education-focused, academic clinician with sub-specialist interest in all aspects of triple negative breast cancer (TNBC) and young women with breast cancer. Prof. Dent achieved her MD from McMaster University in Hamilton, Ontario, Canada and then completed her internal medicine and medical oncology residency at the Princess Margaret Hospital and the Sunnybrook Odette Cancer Center in Toronto, Canada. This was followed by a fellowship in breast cancer, supported by a Marion Walker Women’s Health Scholarship, and MSc in Clinical Epidemiology and Statistics at the University of Toronto. During her training Prof Dent was fortunate to have completed electives across Canada, the US (Memorial Sloan Kettering), France (Institut Marie Curie) and the Philippines (Philippine General Hospital). In her North American academic career, Prof Dent served as Chair of the locally advanced breast cancer program and Head, Breast Cancer Clinical Trials Unit at the Sunnybrook Odette Cancer Center from 2008-2011. Her seminal publication whilst in Toronto was a Clinical Cancer Research publication, one of the first to describe what is now known as triple negative with almost 5,500 citations for this individual paper (Dent R et al. Clin Ca Res 2007). She was the PI of one of the first Phase I PARP inhibitor trials in unselected TNBC in combination with taxane chemotherapy and she served as a reviewer for the National Cancer Institute of Canada (NCIC) grants committee. As a consultant at the Sunnybrook Odette Cancer Center, she supervised a number of residents and fellows and was awarded an Outstanding Teaching Award by the University of Toronto. Prof Dent has participated in the ASCO Leadership Development Program and served on a number of ASCO Committees: Education including Chair, Breast Track and Member of the Breast Scientific Committee (ER/HER2 track), as well as on the Editorial Board of the Journal of Clinical Oncology (JCO). In February 2011, Prof Dent moved to Singapore where she is now senior consultant at the National Cancer Center in Singapore (NCCS). Recognizing the need for pan-Asian regional educational interaction Prof Dent co-founded and co-chaired nine Asia Pacific Breast Cancer Summits (https://apbcs.org). Consequently Prof Dent was involved in the establishment of the ESMO Asia meeting subsequently serving as Scientific Chair and Co-Chair Breast Track. Prof Dent has co-chaired the ESMO Breast Preceptorship in Singapore since 2017 and sits on the pan-Asian ESMO adapted guidelines committee as well as the Advanced Breast Cancer ESMO guideline committee. Prof Dent serves as a scientific committee member of the ASCO Breakthrough Asia Meeting. Prof Dent is currently Chair of the ESMO Nomination Committee and a member of the ESMO Council. Prof Rebecca Dent has over 18,000 citations  and an  h-index over 50. She sits on the Editorial Board of The Lancet Oncology. She has been invited as an oral and plenary discussant at ESMO as well as an invited speaker at numerous meetings for ASCO, ESMO Asia, and other meetings across Asia such as the Japanese Society of Medical Oncology and Korean Society of Medical Oncology. Prof Dent is a steering committee member and PI for a number of large international trials evaluating novel agents in the treatment of TNBC. Funding was secured for a novel investigator initiated global study evaluating the role of PARP inhibition with or without immune checkpoint inhibition in platinum sensitive TNBC which has just completed recruitment in the US, Korea and in Singapore (The DORA study). This is a pivotal Duke NUS Singapore and Duke USA collaboration. As of October 2018, Prof Dent has been Head of the department of Medical Oncology at the National Cancer Center Singapore (NCCS) at SingHealth. NCCS has recently been designated as a comprehensive cancer center and Prof Dent was appointed Chairman of the Division of Medical Oncology in 2021. Prof Dent maintains a busy clinical practice, as well as teaching medical students at Duke-NUS. This has been recognized with a star award for Quality National Service and the SingHealth Outstanding Clinician Award. Most recently in 2023 she was one of the Singapore National Health Quality Service Superstar award winners.    

Audio Journal of Oncology interview with: Bart Neyns MD PhD, Vrije Universiteit Brussel, Faculty of Medicine and Pharmacy, Medical Oncology Department, Brussels, Belgium  BARCELONA, Spain—Intracranial administration of autologous dendritic cells was combined with combination checkpoint inhibition in a phase 1 study of patients with recurrent glioblastoma that reported marked clinical responses to the European Society for Medical Oncology (ESMO) annual meeting in Barcelona. Cells harvested from each patient were injected directly into the brain tissue resection cavity lining after surgery. Patients also received intra-cranial injections of the checkpoint inhibitor combination: nivolumab plus ipilimumab. At the conference, Peter Goodwin discussed the research with lead author of the study, Bart Neyns MD PhD, Head of Medical Oncology at the Vrije Universiteit, Brussel, in the University Hospital Brussels Faculty of Medicine & Pharmacy, Brussels, Belgium. Audio Journal of Oncology interview with: Bart Neyns MD PhD, Vrije Universiteit Brussel, Faculty of Medicine and Pharmacy, Medical Oncology Department, Brussels, Belgium IN : “Patients with recurrent glioblastoma ….  OUT:…from me, Peter Goodwin, goodbye 10:54 secs SOURCE: ESMO 2024 Barcelona ESMO Abstract 441O Neyns , Medical Oncology Department, Vrije Universiteit Brussel – Faculty of Medicine & Pharmacy, Brussels, Belgium “A phase I clinical trial on the intracranial administration of autologous CD1c(BDCA-1)+/CD141(BDCA-3)+ myeloid dendritic cells (myDC) in combination with ipilimumab (IPI) and nivolumab (NIVO) in patients with recurrent high-grade glioma (rHGG)” Reference: CNS tumours Volume 35, Supplement 2S406-S407 September 2024Authors: Neyns1 ∙ I. Dirven1 ∙ L. Lescrauwaet2 ∙ M. Cammaert1 ∙ W. Geens2 ∙ X. Geeraerts1 ∙ L. Stevens1 ∙ S. Brock3 ∙ M. Kockx4 ∙ H. Everaert5 ∙ A-M. Van Binst6 ∙ S. Tuyaerts1 ∙ J. Duerinck7 1. Medical Oncology Department, Vrije Universiteit Brussel – Faculty of Medicine & Pharmacy, Brussels, Belgium 2. Neurosurgery, UZ Brussel – Universitair Ziekenhuis Brussel, Jette, Belgium 3. Pathology, UZ Brussel – Universitair Ziekenhuis Brussel, Jette, Belgium 4. Pathology Department, CellCarta, Antwerpen, Belgium 5. Nuclear Medicine, Vrije Universiteit Brussel – Faculty of Medicine & Pharmacy, Brussels, Belgium 6. Radiology Department, Vrije Universiteit Brussel – Faculty of Medicine & Pharmacy, Brussels, Belgium 7. Neurosurgery Department, Vrije Universiteit Brussel – Faculty of Medicine & Pharmacy, Brussels, Belgium https://www.audiomedica.com/wp-content/2025/09/241011-Bart-Neyns-ESMO-AJO-PRODUCTION-MASTER.mp3Background Intracranial admin of NIVO and IPI following the resection of rHGG is safe and has resulted in encouraging survival (J Duerinck et al. JITC 2021). myDC play a pivotal role in initiating an adaptive anti-tumor immune response and licensing of immune anti-tumor effector cells within the tumor microenvironment. Methods rHGG pts (after prior RT and TMZ, <8 mg methylprednisolone QD), underwent a leukapheresis followed by isolation/cryopreservation of myDC. NIVO (10 mg IV) was administered preoperatively. myDC (5-, 10-, or 20.106 cells) were injected into the brain tissue lining the resection cavity (iCer) following a maximal safe resection (MSR) or intratumorally (iTum) following a stereotactic biopsy (STX). IPI (5 mg) plus NIVO (10 mg) were co-injected iCer or iTum with the myDC. Postoperative NIVO was administered intracavitary (iCav, 10 mg) and intravenously (IV, 10 mg) Q2w (max 11x). Results 21 pts (13 M; med 49 y [range 20 -78]; IDHwt 17 pts, ECOG PS 0 or 1: 18-, 3 pts) underwent procurement of myDC; intraoperative administration of myDC was preceded by MSR in 19 pts, and STx in 2 pts. Respectively 6, 3, and 12 pts were treated at the 3 myDC dose levels. All pts received the peri-op iTum/iCer/IV-admin of IPI and NIVO as planned. The median postop iCav and IV NIVO-admin was 7 (range 0-11) and 8 (0-11). Study treatment was discontinued early for PD in 9- and AE in 3 pts. Most important TRAEs: bacterial colonization of the Ommaya reservoir (n=4), craniotomy wound dehiscence (n=2), and bacterial meningitis (n=1). At DBL (01MAY2024), 6 pts (29%) remain progression-free (incl. 3 pts with >2y PFS). PFS (med. 24w [95% CI 8- 39]) is superior when compared to the pts (n=70) with resectable rHGG treated in 4 other cohorts of the GlITIpNi trial (p=0.003). When including the durable benefit from bevacizumab at first PD in 3 pts, PFS compared favorably to a historical pooled cohort (n=469) of rHGG treated with VEGF(R)-inhibitors (p=0.007). The 1-year OS-rate was 50% [95% CI 24-76]. Conclusions Intracranial administration of myDC combined with IPI/NIVO is feasible, safe and associated with encouraging survival, deserving further investigation.          

An interview with: Victor Velculescu MD PhD, Co-director, Cancer Genetics & Epigenetics Program, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. SAN DIEGO, USA—A blood test using an artificial intelligence DNA pattern recognition system that brings earlier, more certain detection of ovarian cancer was reported at the American Association for Cancer Research Annual Meeting held in San Diego. The test analyses patterns of fragments of circulating DNA (called DNA fragmentomes). When combined with analysis of circulating tumor protein markers these were found to be highly correlated with ovarian cancer. The test uses the DELFI (DNA Evaluation of Fragments for early Interception) system that has already been established for early detection of lung cancer. At the San Diego conference lead author of the research, Victor Velculescu MD PhD, Co-director, Cancer Genetics & Epigenetics Program, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland discussed the findings with Peter Goodwin. AUDIO JOURNAL OF ONCOLOGY with: Victor Velculescu MD PhD. IN: “Hello, Peter Goodwin here …..OUT:  ……..for the Audio Journal of Oncology, I’m Peter Goodwin”   13:49secs 2024 AACR ABSTRACT: Abstract 773: Early detection of ovarian cancer using cell-free DNA fragmentomes  AUTHORS: Akshaya V. Annapragada; Jamie E. Medina; Victor E. Velculescu et al. https://aacrjournals.org/cancerres/article/83/7_Supplement/773/719566/Abstract-773-Early-detection-of-ovarian-cancer https://pubmed.ncbi.nlm.nih.gov/39345137/ Early Detection of Ovarian Cancer Using Cell-Free DNA Fragmentomes and Protein Biomarkers Jamie E Medina # 1, Akshaya V Annapragada # 1, Pien Lof 2, Sarah Short 1, Adrianna L Bartolomucci 1, Dimitrios Mathios 1, Shashikant Koul 1, Noushin Niknafs 1, Michaël Noë 1, Zachariah H Foda 1, Daniel C Bruhm 1, Carolyn Hruban 1, Nicholas A Vulpescu 1, Euihye Jung 3, Renu Dua 1, Jenna V Canzoniero 1, Stephen Cristiano 1, Vilmos Adleff 1, Heather Symecko 4, Daan van den Broek 5, Lori J Sokoll 1, Stephen B Baylin 1, Michael F Press 6, Dennis J Slamon 7, Gottfried E Konecny 7, Christina Therkildsen 8, Beatriz Carvalho 9, Gerrit A Meijer 9, Claus Lindbjerg Andersen 10 11, Susan M Domchek 3 4, Ronny Drapkin 3 4, Robert B Scharpf 1, Jillian Phallen 1, Christine A R Lok 2, Victor E Velculescu 1 Affiliations 1The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. 2Department of Gynecologic Oncology, Centre of Gynecologic Oncology Amsterdam, Antoni van Leeuwenhoek Hospital-The Netherlands Cancer Institute, Amsterdam, the Netherlands. 3Penn Ovarian Cancer Research Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. 4Basser Center for BRCA, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania. 5Department of Laboratory Medicine, Antoni van Leeuwenhoek Hospital-The Netherlands Cancer Institute, Amsterdam, the Netherlands. 6Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California. 7David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California. 8Department of Surgical Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark. 9Department of Pathology, Antoni van Leeuwenhoek Hospital-The Netherlands Cancer Institute, Amsterdam, the Netherlands. 10Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark. 11Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.   Ovarian cancer is a leading cause of death for women worldwide, in part due to ineffective screening methods. In this study, we used whole-genome cell-free DNA (cfDNA) fragmentome and protein biomarker [cancer antigen 125 (CA-125) and human epididymis protein 4 (HE4)] analyses to evaluate 591 women with ovarian cancer, with benign adnexal masses, or without ovarian lesions. Using a machine learning model with the combined features, we detected ovarian cancer with specificity >99% and sensitivities of 72%, 69%, 87%, and 100% for stages I to IV, respectively. At the same specificity, CA-125 alone detected 34%, 62%, 63%, and 100%, and HE4 alone detected 28%, 27%, 67%, and 100% of ovarian cancers for stages I to IV, respectively. Our approach differentiated benign masses from ovarian cancers with high accuracy (AUC = 0.88, 95% confidence interval, 0.83–0.92). These results were validated in an independent population. These findings show that integrated cfDNA fragmentome and protein analyses detect ovarian cancers with high performance, enabling a new accessible approach for noninvasive ovarian cancer screening and diagnostic evaluation. Significance: There is an unmet need for effective ovarian cancer screening and diagnostic approaches that enable earlier-stage cancer detection and increased overall survival. We have developed a high-performing accessible approach that evaluates cfDNA fragmentomes and protein biomarkers to detect ovarian cancer. Introduction Ovarian cancer is a leading cause of death in women worldwide, with more than 300,000 new cases and nearly 200,000 deaths globally each year (1). In the United States during 2024, approximately 19,600 new cases will be diagnosed and 12,700 women will die from ovarian cancer (2). The most common form of ovarian cancer is epithelial ovarian cancer, which comprises four major subtypes: serous, clear cell, mucinous, and endometrioid carcinomas. According to the Surveillance, Epidemiology, and End Results database, for individuals with detected invasive epithelial ovarian cancer, the estimated 5-year survival is 93% and 75% for localized (stage I) or regional (stage II or stage IIIA1 with regional lymph node involvement) disease, respectively, compared with 31% for distant disease (remaining stage III or stage IV; refs. 3, 4). Unfortunately, ovarian cancer is usually detected in advanced stages (stages III and IV) due to nonspecific clinical symptoms at earlier stages and the lack of an effective screening approach (3). Consequently, there is a clear unmet clinical need for the development of highly specific and sensitive assays to detect ovarian cancer in its earliest stages. Ovarian cancer screening trials such as the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (5), the U.K. Collaborative Trial of Ovarian Cancer Screening (UKCTOCS; ref. 6), and the Normal Risk Ovarian Screening Study (ref. 7) have shown that existing biomarkers, including cancer antigen 125 (CA-125), may provide a shift toward detection of earlier stages of cancer but not a survival benefit, likely because of suboptimal detection of ovarian cancers. These analyses open the door to new and more effective approaches aimed at identifying combinations of biomarkers with improved performance for early ovarian cancer detection. Such approaches would need to be affordable, accessible, and have high performance for high-grade serous ovarian carcinoma (HGSOC), which is more aggressive, typically detected in late stages, and responsible for the majority of ovarian cancer deaths (8). A secondary clinical need also exists in determining whether women presenting with ovarian masses have benign or malignant lesions. In this setting, preoperative malignancy classification is challenging and may lead to unnecessary procedures. A number of biomarkers have been proposed in this setting, including CA-125 and human epididymis protein 4 (HE4; refs. 9–11). Prediction models using a combination of multiple protein biomarkers as well as age and menopausal status (12), the risk of malignancy index (ref. 13), and other ultrasound classifications (International Ovarian Tumor Analysis; ref. 14) have been developed, but these vary in accuracy, performance, and ease of use in a clinical setting. Analyses of circulating cell-free DNA (cfDNA) provide another approach for early cancer detection in the screening or diagnostic settings. Approaches for ovarian cancer have included identification of tumor-specific mutations (15, 16), or alterations in DNA methylation (17), or specific repeat sequences (18, 19); however, these approaches have had limited sensitivities for early-stage disease, may be confounded by alterations in white blood cells (20), and have not been validated for clinical use. An emerging approach of cfDNA analyses have focused on the “cfDNA fragmentome,” defined as the genome-wide compendium of cfDNA fragments in the circulation, providing an integrated view of the chromatin, genome, epigenome, and transcriptome states of normal and cancer cells of an individual. Recent cfDNA fragmentome analyses using low-coverage whole-genome sequencing (WGS) combined with machine learning using DNA evaluation of fragments for early interception (DELFI) have demonstrated high sensitivity for early detection across lung (21), liver (22), and other cancer types (23–26) using an accessible, cost-efficient approach (27) that is not confounded by clonal hematopoiesis (20, 28). In this study, we present a method to detect ovarian cancer using cfDNA fragmentomes combined with protein biomarkers. This multianalyte combination has the benefit of utilizing genome-wide multifeature fragmentation analyses together with complementary protein biomarkers CA-125 and HE4 from the same blood draw that may have utility in both the screening and diagnostic settings. Results Clinical Cohorts Blood samples in the discovery cohort were collected from women with ovarian cancer (n = 94), with benign adnexal masses (n = 203), or without any known ovarian lesions (n = 182), who were part of previously reported prospective diagnostic or screening efforts at hospitals in the Netherlands and Denmark (Table 1; Supplementary Table S1; refs. 9, 21, 23, 29). For the validation cohort, we analyzed samples from patients prospectively collected at the University of Pennsylvania or t

Audio Journal of Oncology: Sept 23rd, 2025 An interview with: Timothy Yap MD PhD MBBS, Professor of Investigational Cancer Therapeutics, Head of Clinical Development, Therapeutics Discovery Division, University of Texas MD Anderson Cancer Center, Houston, USA SAN DIEGO, USA—Breast, ovarian, pancreatic, prostate and other solid tumors with mutations sensitizing them to poly ADP ribose polymerase (PARP) inhibition, could potentially be controlled better and with less toxicity with the new selective PARP-1 inhibitor saruparib than with existing licensed agents which inhibit both PARP 1 and PARP 2. That’s according to early results from the PETRA study reported to the San Diego meeting of the American Association for Cancer Research (AACR). Timothy Yap MD PhD MBBS, Professor of Investigational Cancer Therapeutics and Head of Clinical Development in the Therapeutics Discovery Division of the University of Texas MD Anderson Cancer Center in Houston, reported early clinical data from the PETRA study.  After his talk at the AACR conference he discussed the findings with Peter Goodwin. Timothy Yap MD PhD MBBS: AUDIO JOURNAL OF ONCOLOGY: IN (SARAH M AXWELL):  A new class of PARP inhibitor … ….OUT:  from me, Sarah Maxwell, Good-bye. 18:45 secs WHAT IS SARUPARIB? : “Saruparib is an investigational new drug that is being evaluated for the treatment of cancer. It is a first-in-class selective inhibitor of poly-ADP ribose polymerase 1, designed to treat cancers with homologous recombination repair deficiencies as a result of mutations in BRCA1, BRCA2, PALB2, RAD51C, or RAD51D genes.” AACR ABSTRACT: Next-generation PARP Inhibitor Demonstrates Clinical Benefit in Patients with Homologous Recombination Repair-deficient Breast Cancer PETRA: first-in-human Phase 1/2a trial of the first-in-class new generation poly-ADP-ribose polymerase-1 selective inhibitor (PARP1i) saruparib (AZD5305) in patients (pts) with advanced solid tumors with BRCA1/2, PALB2 or RAD51C/D mutations https://aacrjournals.org/cancerres/article/82/12_Supplement/CT007/701955/Abstract-CT007-PETRA-First-in-class-first-in-human AACR Abstract CT007: PETRA: First in class, first in human trial of the next generation PARP1-selective inhibitor AZD5305 in patients (pts) with BRCA1/2, PALB2 or RAD51C/D mutations Abstract Background: AZD5305 is a potent, highly selective PARP1 inhibitor and trapper with superior preclinical tolerability, target engagement and efficacy vs 1st generation dual PARP1/2 inhibitors (PARPi). This is the first report of the ongoing Phase 1/2a PETRA (NCT04644068) trial. Citation Format: Timothy A. Yap, Seock-Ah Im, Alison M. Schram, Adam Sharp, Judith Balmana, Richard D. Baird, Jessica S. Brown, Maria Schwaederle, Elizabeth A. Pilling, Ganesh Moorthy, Spiros Linardopoulos, Adam Dowson, Carol Pound, Edit Lukacs, Sabina Cosulich, Stephen J. Luen. PETRA: First in class, first in human trial of the next generation PARP1-selective inhibitor AZD5305 in patients (pts) with BRCA1/2, PALB2 or RAD51C/D mutations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT007. Methods: Pts with advanced breast, ovarian, prostate or pancreatic cancer bearing germline or somatic BRCA1/2, PALB2 or RAD51C/D mutations received AZD5305 QD PO until disease progression. ECOG PS 0-2 and Hb ≥9.0 g/dL were required. Prior PARPi and platinum therapy were permitted. The primary objective was safety; secondary objectives included pharmacokinetics (PK) and pharmacodynamics in tumor and/or blood samples and response by RECIST v1.1, CA125 or PSA. Exploratory genomic analyses included zygosity evaluation and ctDNA response monitoring. Results: At data cutoff (Nov 17, 2021), 46 pts received AZD5305 10-90 mg QD (43.5% had prior PARPi; median 3.5 prior lines of therapy). AZD5305 was well tolerated across all doses without DLTs. PK exposures were dose-proportional. Steady-state Ctrough was higher than 1st generation PARPi: specificaly 6.3 and 31.9 fold above target effective concentration at 10 and 90 mg, respectively. PARylation inhibition was ≥90% at 10-40 mg QD (PBMCs) confirming target engagement. 7/25 (28%) pts had objective responses: 5 RECIST PRs (3 confirmed) and 2 additional pts with PSA50 responses (1 confirmed), including platinum- and PARPi-resistant pts. 13/22 (59%) RECIST-measurable pts had SD or PR up to 51+ weeks. ctDNA declined on treatment in 7/13 (54%) evaluable pts (3 complete, 4 >50% reductions) across doses. Conclusions: AZD5305 is a highly selective PARP1 inhibitor and trapper with excellent physiochemical properties and a wide therapeutic index. It led to maximal target engagement and showed promising clinical activity with favorable tolerability at exposures surpassing those of 1st generation PARPi. MORE: (AACR RELEASE): Next-generation PARP Inhibitor Demonstrates Clinical Benefit in Patients with Homologous Recombination Repair-deficient Breast Cancer Drug has higher selectivity for PARP1, improving safety and tolerability SAN DIEGO – Saruparib, a selective inhibitor of poly-ADP ribose polymerase 1 (PARP1), demonstrated a promising objective response rate and progression-free survival in patients with certain homologous recombination repair (HRR)-deficient breast cancers, according to results from the phase I/II PETRA trial, presented at the American Association for Cancer Researc 2024 Annual Meeting in San Diego. Although blocking the enzyme PARP1 may be sufficient to prevent DNA repair in HRR-deficient tumors, all PARP inhibitors currently approved by the U.S. Food and Drug Administration (FDA) block both PARP1 and PARP2, which can limit utility because of toxicity, explained Timothy A. Yap, MBBS, PhD, professor of Investigational Cancer Therapeutics and vice president and head of clinical development in the Therapeutics Discovery Division at The University of Texas MD Anderson Cancer Center, who presented the study. “When we were developing first-generation PARP inhibitors, we weren’t able to increase the doses above a certain threshold because of toxicity,” Yap said. “By designing selective PARP1 inhibitors, we have a great opportunity to improve safety, tolerability, pharmacokinetics, pharmacodynamics, efficacy, and combinability with other therapies.” Saruparib, a PARP1-specific inhibitor, showed promising tumor growth inhibition in preclinical models of breast ovarian pancreatic and prostate cancer harboring HRR deficiency mutations. Because saruparib was less toxic than other PARP inhibitors, it could be given at higher doses. “The properties of saruparib enable patients to reach high drug pharmacokinetic exposure levels and pharmacodynamic target engagement,” Yap said. “This means that patients may be able to stay on the optimal dose for a longer duration due to fewer dose interruptions and reductions, which may ultimately improve efficacy.” PETRA is a multicenter phase I/II clinical trial evaluating the safety, tolerability, and efficacy of saruparib in 306 patients with previously treated (including ≤1 prior PARP inhibitor in the dose escalation phase and PARP inhibitor-naive breast cancer patients in the dose expansion phase) HRR-deficient breast, ovarian, pancreatic, or prostate cancer. Patients had tumors with mutations in one of five HRR genes: BRCA1, BRCA2, PALB2, RAD51C, or RAD51D. Patients were treated at doses ranging from 10 to 140 mg saruparib daily; 60 mg daily was chosen as the recommended dose for further clinical development. Among the 31 breast cancer patients treated with 60 mg saruparib, the objective response rate was 48.4%, the median duration of response was 7.3 months, and the median progression-free survival was 9.1 months. In the cohort of 141 patients who received the 60 mg dose across all cancer types, adverse events were observed in 92.2% of patients and 12.1% of patients experienced a serious adverse event. Adverse events related to saruparib were observed in 76.6% of patients, and 2.1% of patients had a serious adverse event related to the drug; 3.5% of patients discontinued treatment due to adverse events related to saruparib. Yap noted that the adverse events profile from this phase I/II trial of heavily pretreated patients compared favorably to those from phase III trials testing other PARP inhibitors in treatment-naïve patients. “The low rate of dose reductions observed with saruparib suggests a very manageable safety profile that we believe will enable patients to stay longer at the optimal dose and therefore maximize the opportunity for long-term benefit,” Yap said. Pharmacokinetic analyses showed that, at all dose levels, patients maintained higher blood concentrations of saruparib than typically observed with other PARP inhibitors. At the molecular level, saruparib inhibited around 90% of PARP activity in tumor tissue collected from biopsies. “The excellent safety and tolerability profile, along with the favorable pharmacokinetic and pharmacodynamic properties, may enable patients to remain on saruparib treatment with sustained maximal target engagement and limited dose reductions or discontinuation,” Yap said. Limitations of this study include its single-arm design and small sample size. This study was funded by AstraZeneca. Yap is head of clinical development in the Therapeutics Discovery Division at The University of Texas MD Anderson Cancer Center, which has licensed therapeutics to Artios Pharma. He serves or has served as a consultant for 858 Therapeutics, Inc., AbbVie, Acrivon Therapeutics, Adagene, Aduro Biotech, Inc., Almac,  Amgen, Amphista Therapeutics, Artios Pharma, Astex Pharmaceuticals, AstraZeneca, Athena Therapeutics, Atrin Pharmaceuticals, Avenzo Therapeutics, Avoro Capital Advisors, Axiom Real-Time Metrics, Baptist Health System, Bayer, BeiGene, BioCity Biopharma, Blueprint Medicines, Boxer Capital, BridGene Biosciences, Bristol Myers Squibb, C4 Therapeutics, Inc., Cal

Interviews with: Stacey A.  Kenfield ScD, Epidemiologist, Professor of Urology, Epidemiology and Biostatistics, and June Chan ScD, Cancer Epidemiologist, Department of Epibiostat and Urology, University of California San Francisco, California USA.  SAN DIEGO, USA—Physical exercise keeps patients with prostate cancer alive longer, according to a combination of epidemiological and clinical study evidence emerging from research in San Francisco, California. Intervention study findings reported at the American Association for Cancer Research (AACR) Annual Meeting in San Diego are consistent with mounting epidemiological evidence showing that regular physical exercise can help patients with advanced or metastatic prostate cancer live longer, have slower disease progression and improve their quality of life. Stacey A. Kenfield ScD, Professor of Urology, Epidemiology and Biostatistics at the University of California San Francisco (UCSF) reported from the INTERVAL-GAP4 trial. Together with her colleague, June Chan ScD, Cancer Epidemiologist in the Department of Epibiostat and Urology at UCSF (who chaired the session on exercise for cancer patients at the AACR) she talked with the Audio Journal of Oncology about the findings and recommendations for using physical exercise as an adjunct to standard management for patients with prostate cancer. Audio Journal of Onclogy Episode: Stacey A. Kenfield ScD and June Chan ScD, University of California San Francisco IN (Sarah Maxwell): There’s new evidence that exercise….. OUT:  From me, Sarah Maxwell, Bye bye!”  10:28 secs AACR ABSTRACT TITLE: Intense exercise for survival among men with metastatic prostate cancer: 12-month feasibility results from the INTERVAL-GAP4 trial pilot site at Edith Cowan University, Australia First Author: Stacey A. Kenfield, UCSF – University of California San Francisco, San Francisco, CA, Authors: A. Kenfield1, N. H. Hart2, J. Sison1, J. M. Chan1, K. S. Courneya3, F. Saad4, R. U. Newton5; Institutions: 1UCSF – University of California San Francisco, San Francisco, CA, 2University of Technology Sydney, Sydney, Australia, 3University of Alberta, Edmonton, AB, Canada, 4Université de Montréal, Montréal, QC, Canada, 5Edith Cowan University,  Perth, Australia Stacey A. Kenfield, Departments of Urology and Epidemiology & Biostatistics, University of San Francisco California, San Francisco, CA ABSTRACT Introduction: Men with prostate cancer undertaking moderate-to-vigorous exercise have a marked reduction of 30-60% in all-cause and cancer-related mortality based on observational studies. In 2016, the Intense Exercise for Survival among Men with Metastatic Prostate Cancer (INTERVAL-GAP4) was launched to determine if supervised exercise improves overall survival in men with metastatic prostate cancer. Here, we describe the demographic characteristics, completion rates, exercise adherence, and safety of the first 12 months of the intervention at the pilot site, Edith Cowan University in Perth, Australia. Methods: INTERVAL-GAP4 is a multi-center global randomized controlled phase III trial. Patients are randomly allocated (1:1) to: (intervention) a high intensity combined resistance and aerobic exercise supervised program for 1 year tapering to self-management in year 2; or (control) self-directed unsupervised exercise with print materials. Patients were stratified by site and by disease/treatment status (metastatic hormone-sensitive prostate cancer [mHSPC] or metastatic castration-resistant prostate cancer [mCRPC] and if the latter, treatment modality). The study did not meet recruitment goals and closed to further enrollment in February 2023. Results: 240 participants were evaluated between April 2016-Feb 2023, 60 patients were consented, 52 participants were randomized, and two patients did not receive the allocation, resulting in 50 participants (27 intervention and 23 control). Main reasons for exclusion were not meeting clinical criteria (N=81), time commitment (N=24), unable to contact (N=22), not interested (N=19), and poor physical function (N=13). Median age at randomization was 72 years (IQR: 68, 77), median body mass index (BMI) was 31.7 kg/m2 (IQR: 27.5, 35.7), 94% identified as white, and time since diagnosis was 5 years (IQR: 1, 9). 13 participants (26%) had mHSPC and 37 (74%) had mCRPC. Completion rates were the following at 6 months: 84% completed surveys, 62% exercise testing, and 66% biological samples. Of 42 alive at 12 months: 85% completed surveys, 73% testing, and 73% biological samples. Median exercise adherence was 90% (IQR: 78, 97) for the first 12 months of the study. Adherence was not significantly different for those with mCRPC vs. mHSPC status. There were 10 SAEs in first 12 months; all (100%) were unrelated to the intervention. Conclusions: Exercise training was feasible and safe in men with metastatic prostate cancer with no difference observed in exercise session adherence by disease status. Survey completion was high, while in-person completion rates were affected by the COVID-19 pandemic. Additional analysis of the entire study population (N=145) is ongoing and will be compared with the pilot site. ALSO: https://ascopubs.org/doi/10.1200/GO.2023.9.Supplement_1.81 Intense exercise for survival among men with metastatic prostate cancer: 12 months feasibility results from the INTERVAL-GAP4 trial. Background: Exercise is now considered an important therapy to ameliorate treatment side effects, improve quality of life and physical function however, causation of survival benefit and the underlying mechanisms is not yet established. In 2015, the Intense Exercise for Survival among Men with Metastatic Castrate-Resistant Prostate Cancer (INTERVAL-GAP4) – a worldwide multicentre phase III trial – was launched to determine if high-intensity combined resistance and aerobic exercise plus psychosocial support improves overall survival in men with metastatic prostate cancer. Here, while exercise delivery and follow-up assessments are still taking place in 6 different countries, we aim to examine the feasibility, exercise compliance and safety of a 12-month exercise medicine program in patients with mCRPC. Methods: Experimental design was a longitudinal analysis of attrition rates, exercise attendance and compliance metrics and programme safety over the initial 12 months of patients participating in the INTERVAL-GAP4 trial at the Edith Cowan University site in Perth, Australia. Results: 201 patients were screened for participation and 46 patients (22.9%) were randomly assigned to the two study arms. Median time since prostate cancer diagnosis was 72.0 (interquartile range (IQR): 19.5-118.5) months. Most patients were previously treated with radiotherapy (53.3%). Metastases present mostly in the lymph nodes (53.3%), followed by bones (51.1%), lungs (2.2%) and bladder (2.2%). Participants attended a total of 2,907 out of 3,744 exercise sessions scheduled, with a median exercise attendance of 78.8% (IQR: 71.6%-82.7%) per participant. Majority of sessions were performed at an RPE of 7-8 indicating “vigorous intensity” or at an RPE of 5-6 indicating “moderate intensity” (67.2%). Tolerance was moderate-to-high in most sessions (83.0%). 191 adverse events (AEs) were observed throughout the study period. A total of 136 adverse events were reported by 19 participants from the exercise group, and these were mainly disease related (n= 69, 50.7%). Most AEs were grade 1 and 2 (n= 126, 92.7%). In the control group, 55 AEs were observed, and these were mainly disease related (n= 22, 40.0%) and grade 1 and 2 (n= 51, 92.7%). The most common intervention-related adverse events experienced in the exercise group were pain (n= 6, 50.0%; i.e., back pain, bone pain, lymph node pain, and general pain). Conclusions: Patients with mCPRC can participate in high-intensity aerobic and resistance training with moderate to high attendance and tolerance. The exercise intervention appears safe with limited intervention-related adverse events experienced and mostly minor and expected. However, with only 22.9% of screened patients deemed suitable and willing, this aspect of feasibility requires attention. Clinical trial information: NCT02730338. Robert Usher Newton: Exercise Medicine Research Institute, Edith Cowan University, Joondalup, Western Australia, Australia Pedro Lopez Nicolas H. Hart Daniel Abido Galvao Dennis R Taaffe Timothy Dudley Clay Charles M Ryan Stacey A. Kenfield Fred Saad: Division of Urology, Centre Hospitalier de l’Université de Montréal (CHUM/CRCHUM), Montreal, QC, Canada