Oncology Knowledge into Practice Podcast

Rearranged during transfection (RET) and tropomyosin receptor kinase (TRK) fusions are involved in various adult and paediatric cancers, including thyroid cancers. There is a high mortality rate for some of these cancers, partly due to the lack of efficient detection, diagnosis, and prognosis. The US and European guidelines recommend genomic testing as a part of standard diagnostic evaluations for some cancers to identify driver mutations for which effective therapies or clinical trials are available. However, adherence to genomic testing guidelines presents challenges to practitioners, including coordination of sample handling, long turnaround times, test reimbursement (in applicable settings), access to targeted therapies, insufficient tissue, and patient harm from the repeat biopsies necessary if the tissue sample is insufficient. This episode offers some guidance around when and how to test for biomarkers of response to precision medicines. To answer our questions on the topic, we welcome the expertise of Professor Fernando López-Ríos. Professor López-Ríos is a pathologist at the ‘12 de Octubre’  University Hospital in Spain. Funding Information: This episode is supported by an educational grant from Eli Lilly, who have had no influence on the content or choice of faculty. References 1. National Comprehensive Cancer Network. Thyroid Carcinoma. (Version 3.2021-October 15, 2021). Available at: https://www.nccn.org/professionals/physician_gls/pdf/thyroid.pdf. Accessed January 16, 2022. 2. Belli C, et al. ESMO recommendations on the standard methods to detect RET fusions and mutations in daily practice and clinical research. Ann Oncol. 2021 Mar;32(3):337-350. 3. Marchiò C, et al. ESMO recommendations on the standard methods to detect NTRK fusions in daily practice and clinical research. Ann Oncol. 2019 Sep 1;30(9):1417-1427. 4. OncoKB: MSK's Precision Oncology Knowledge Base. Available at: https://www.oncokb.org/. Accessed March 15, 2022. 5. Mosele F, et al. Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group. Ann Oncol. 2020 Nov;31(11):1491-1505.

In today’s episode, we’re going to talk about how precision medicine fits into thyroid cancer treatment guidelines. To answer our questions on this topic, we welcome the expertise of Dr. Lori Wirth. Dr. Wirth is Medical Director of the Center for Head and Neck Cancers at the Massachusetts General Hospital, and an Associate Professor in Medicine at Harvard Medical School. Funding statement: This independent educational activity is supported by an educational grant from Eli Lilly. The educational content has been developed by Liberum IME in conjunction with an independent steering committee; Eli Lilly has had no influence on the content of this education. References:   Filetti S, Durante C, Hartl D, et al. Thyroid Cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019; 30:1856-1883.  National Comprehensive Cancer Network. Thyroid Carcinoma. (Version 3.2021-October 15, 2021). Available at: https://www.nccn.org/professionals/physician_gls/pdf/thyroid.pdf. Accessed January 16, 2022.  Fleeman N, Houten R, Chaplin M, et al. A systematic review of lenvatinib and sorafenib for treating progressive, locally advanced or metastatic, differentiated thyroid cancer after treatment with radioactive iodine. BMC Cancer. 2019;19:1209. https://doi.org/10.1186/s12885-019-6369-7  Naoum GE, Morkos M, Kim B, Arafat W. Novel targeted therapies and immunotherapy for advanced thyroid cancers. Mol Cancer. 2018;17:51.   Pekova B, Sykorova V, Mastnikova K, et al. NTRK fusion genes in thyroid carcinomas: Clinicopathological characteristics and their impacts on prognosis. Cancers.2021;13:1932. https://www.mdpi.com/2072-6694/13/8/1932  Pitoia F. Complete response to larotrectinib treatment in a patient with papillary thyroid cancer harboring an ETV6-NTRK3 gene fusion. Clin Case Rep. 2021;9:1905-1912. doi: 10.1002/ccr3.3900   VITRAKVI, Prescribing information. Bayer HealthCare Pharmaceuticals Inc. Revised: March 2021.  ROZLYTREK, Prescribing information. Genentech USA, Inc. Revised: November 2021.  Hong DS, DuBois SG, Kummar S, et al. Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol. 2020;21:531-540.  Chu YH, Dias-Santagata D, Farahani AA, et al. Clinicopathologic and molecular characterization of NTRK-rearranged thyroid carcinoma (NRTC). Mod Pathol. 2020;33:2186-2197.   Doebele RC, Drilon A, Paz-Ares L, et al. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1–2 trials. Lancet Oncol. 2020;21:271-282.   RETEVMA, Prescribing information. Lilly USA, LLC. Initial US approval: 2020.  GAVRETO, Prescribing information. Genentech USA, Inc. and Blueprint Medicines Corporation. Revised: April 2021.  Krajewska J, Kukulska A, Oczko-Wojciechowska M, Jarzab B. Recent advances in precision medicine for the treatment of medullary thyroid cancer. Expert Review of Precision Medicine and Drug Development. 2021;6(5): 307-315. https://doi.org/10.1080/23808993.2021.1964952   European Medicines Agency. Retsevmo. December 11, 2020. Accessed January 18, 2022. https://www.ema.europa.eu/en/medicines/human/EPAR/retsevmo  European Medicines Agency. Gavreto. September 17, 2021. Accessed January 18, 2022. https://www.ema.europa.eu/en/medicines/human/EPAR/gavreto 

Precision medicine is a promising field that’s opening doors to novel therapeutics for many patients. But how does it fit into thyroid cancer specifically? What treatments are available or in the pipeline, for which patient subgroup, and what are the potential benefits? We’ll start off our series by exploring these questions, and we’ve invited Dr Eric Sherman, medical oncologist and thyroid cancer expert at the Memorial Sloan Kettering Cancer Center in New York, to provide his insights. Funding statement: This independent educational activity is supported by an educational grant from Eli Lilly. The educational content has been developed by Liberum IME in conjunction with an independent steering committee; Eli Lilly has had no influence on the content of this education. References: American Cancer Society. Key Statistics for Thyroid Cancer. Updated January 12, 2021. Accessed November 23, 2021. American Cancer Society website. https://www.cancer.org/cancer/thyroid-cancer/about/key-statistics.html. Araque KA, Gubbi S, Klubo-Gwiezdzinska J. Updates on the Management of Thyroid Cancer. Horm Metab Res. 2020;52(8):562-577. doi: 10.1055/a-1089-7870. Cancer Connect. Therapies Show Initial Effectiveness in Subset of Papillary Thyroid Cancer. Cancer Connect website. Published July 18, 2018. Accessed December 14, 2021. https://news.cancerconnect.com/thyroid-cancer/therapies-show-initial-effectiveness-in-subset-of-papillary-thyroid-cancer?redir=1. ClinicalTrials.gov website search results: pembrolizumab / Thyroid Cancer / Phase 2. Accessed December 14, 2021. https://clinicaltrials.gov/ct2/results?term=pembrolizumab&cond=Thyroid+Cancer&age_v=&gndr=&type=&rslt=&phase=1&Search=Apply Dabrafenib With or Without Trametinib in Treating Patients With Recurrent Thyroid Cancer. ClinicalTrials.gov identifier: NCT01723202. Updated February 25, 2021. Accessed December 14, 2021. Drilon A, Laetsch TW, Kummar S, et al. Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. N Engl J Med. 2018;378(8):731-739. doi: 10.1056/NEJMoa1714448. Pekova B, Sykorova V, Mastnikova K, et al. NTRK Fusion Genes in Thyroid Carcinomas: Clinicopathological Characteristics and Their Impacts on Prognosis. Cancers. 2021;13(8):1932. doi: 10.3390/cancers13081932. U.S. Food & Drug Administration. FDA approves selpercatinib for lung and thyroid cancers with RET gene mutations or fusions. FDA website. Updated May 11, 2020. Accessed November 23, 2021. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-selpercatinib-lung-and-thyroid-cancers-ret-gene-mutations-or-fusions. U.S. Food & Drug Administration. FDA approves pembrolizumab for adults and children with TMB-H solid tumors. Updated June 17, 2020. Accessed December 14, 2021. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-adults-and-children-tmb-h-solid-tumors#:~:text=The%20recommended%20pembrolizumab%20dosage%20regimen%20for%20TMB-H%20solid,pediatric%20patients.%20View%20full%20prescribing%20information%20for%20KEYTRUDA. U.S. Food & Drug Administration. FDA approves larotrectinib for solid tumors with NTRK gene fusions. FDA website. Updated December 14, 2018. Accessed November 25, 2021. https://www.fda.gov/drugs/fda-approves-larotrectinib-solid-tumors-ntrk-gene-fusions. Weaver CH. Precision Cancer Medicine Treatment of Thyroid Cancers. Cancer Connect website. Published October 24, 2020. Updated September 20, 2021. Accessed November 23, 2021. https://news.cancerconnect.com/thyroid-cancer/precision-cancer-medicine-treatment-of-thyroid-cancers.

In this episode we speak with Dr Navel Daver, Associate Professor, Department of Leukemia, The University of Texas MD Anderson Cancer Center, USA, to get his thoughts on the highlights of ASCO and EHA for patients with MDS and AML. Funding Statement: This series is supported by educational grants from Servier Pharmaceuticals LLC and Takeda, who have had no influence on the content or choice of faculty

At the ASCO and EHA conferences, there were many interesting posters and presentations in the field of haemato-oncology. To share their conference highlights, we’ve invited our ALL expert Dr Dieter Hoelzer, director of internal medicine at the University of Frankfurt in Germany, and our MDS and AML expert Dr Amer Zeidan, Associate Professor Of Internal Medicine at the Yale University School Of Medicine in the US. Funding statement:  This series is supported by educational grants from Servier Pharmaceuticals LLC and Takeda, who have had no influence on the content or choice of faculty