OncoPharm

Looking back at new approvals from 2024 - what to keep, re-gift, or return? And yes, as soon as this was recorded 2 new drugs were approved.

Lots of recent clinical trial updates to discuss: AQUILA: Daratumumab for high-risk smoldering multiple myeloma Checkmate 8HW: Nivo/Ipi for MSI-high/MMRd metastatic colorectal cancer DESTINY-Breast06: T-DXd in HER2-low MBC after hormonal treatment, but without previous chemo for MBC ARMANI: Switch maintenance ramucirumab-paclitaxel in metastatic gastric/GEJ cancer HELEN-006: Neoadjuvant nab-paclitaxel/trastuzumab/pertuzumab vs. TCHP in breast cancer SONIA: finally published!

A first-in-class approval of a bispecific HER2-HER3 monoclonal antibody for NRG1 fusion (+) NSCLC and pancreatic cancer.

The 1st menin inhibitor, revumenib, is approved for relapsed/refractory acute leukemias. Understanding the Pathway: https://doi.org/10.1200/JCO-24-01265

A nice editorial succinctly summarizes a framework for thinking about how to incorporate anthracyclines into the treatment of early stage breast cancer patients. Anthracyclines in Early Breast Cancer: The Long Goodbye -https://doi.org/10.1200/JCO-24-01916 10-year Outcomes of READ trial: https://doi.org/10.1200/JCO.24.00836 Bonus - Practical Guide for Testing for Pharmacogenomics: https://doi.org/10.1200/OP.24.00191

Reviewing the data to support use of dexamethasone solution mouthwash for PIK3/AKT/mTOR inhibitor-induced stomatitis, caused by drugs like everolimus, alpelisib, capivasertib, & inavolisib. SWISH: https://doi.org/10.1016/s1470-2045(17)30109-2 Alliance MIST Trial: https://doi.org/10.1053/j.seminoncol.2023.01.001

The first Cldn 18.2 targeting monoclonal antibody has been improved. Let's talk about it!

Discussing two excellent articles from earlier this month. S1826: N-AVD vs. Bv-AVD (DOI: 10.1056/NEJMoa2405888) & INTERLACE: induction chemo prior to concurrent cisplatin/RT in locally advanced cervical cancer (DOI: https://doi.org/10.1016/S0140-6736(24)01438-7)

A new PIK3Ca inhibitor is approved for breast cancer.

Reviewing 3 recent AML publications Double-Dauno (90 mg/m2 vs. 60 mg/m2): https://doi.org/10.1200/JCO.24.00235 AML60+ Risk Stratification: https://doi.org/10.1200/JCO.23.02631 Decitabine-Ven as bridge to Allo HSCT: https://doi.org/10.1016/S2352-3026(24)00241-2

MSI-high/MMRd rectal cancer treatment guidelines are being re-written. A brief synopsis of why treatment guidelines are changing so quickly in this space. Also, listeners helped out in explaining the ribociclib storage & stability change. Hint: https://www.novartis.com/news/novartis-implements-manufacturing-adjustments-ribociclib-ensure-alignment-latest-regulatory-standards-ebc-end-q2

FDA has been busy the last week approving: -ribociclib x 3 years in high risk stage II & III breast cancer based on the NATALEE trial as well as a new storage requirement -osimertinib indefinitely following chemoradiation in stage III EGFR-mutated NSCLC -amivantamab + chemotherapy following progression on osimertinib (Mariposa-2) -a subcutaneous formulation of atezolizumab -isatuximab + VRD for multiple myeloma -pembrolizumab + chemotherapy for metastatic pleural mesothelioma

Recapping just some of the notable data coming out of ESMO 2024: -Final OS results from Keynote-522 (perioperative pembrolizumab in TNBC) -AMBASSADOR (adjuvant pembrolizumab in bladder cancer) -NIAGRA (perioperative durvalumab in bladder cancer) -ADRIATIC (discussed on ASCO recap Pod, but publication now available) -LEANOX (impact of lean body mass adjustment on oxaliplatin dose)

LMS04 final OS results are published for doxorubicin + trabectedin in Leiomyosarcoma. Plus, a natural experiment of what happens in small cell lung cancer during an IV etoposide shortage. Finally, a nice paper provides some examples of how oncology pharmacists can bridge the care gap between oncology and primary care. LMS04: https://www.nejm.org/doi/pdf/10.1056/NEJMoa2403394 IV etoposide shortage: https://doi.org/10.1200/OP.24.00394 Primary care - oncology pharmacy collaboration: https://doi.org/10.1177/10781552241279303

This is chapter 1 of a keynote address from summer 2024 on putting together the pieces of oncology pharmacy - with an emphasis on how our knowledge of drug dosing changes with time. Video/slides available at YouTube: https://youtu.be/1Oae8AV5Af4

We all know we aren't supposed to make cross-trial comparisons, but it happens anyway. So, let's compare FLARUA2 (osimertinb + chemo) and the newly FDA-approved MARIPOSA regimen (lazertinib + amivantamab) to see what we can (and can't) take away from such a dangerous cross-trial comparison.

A mixed bag of Phase III results for using olanzapine with moderately emegotenic chemotherapy (MEC). Inui, et al: https://doi.org/10.1200/JCO.24.00278 Ostwal, et al: doi:10.1001/jamanetworkopen.2024.26076

A new cellular therapy is approved for synovial sarcoma and the anticipated approval has occurred for the dual IDH1/IDH2 inhibitor, vorasidenib.

FDA appears to change its stance on evaluating perioperative (adjuvant followed by neoadjuvant) ICI study designs in NSCLC. Also, a simple blood test is approved to detect colorectal cancer, but there are several limitations compared to colonoscopy.

Did you know high-dose chemotherapy with autologous stem cel rescue was a "standard" breast cancer treatment ~30 years ago? This story involves changing practices based on Phase II data and outright clinical trial fraud, and retractions of publications. On-site review of Bezwoda study: https://doi.org/10.1016/S0140-6736(00)90024-2 Oral History: https://cancerhistoryproject.com/institutions/nccns-bob-carlson-talks-about-the-day-he-stormed-out-of-a-meeting-with-transplanters/