Oncopharmpod

The 2025 World Conference on Lung Cancer just concluded, and there are several notable updates concerning treatment of EGFR-mutated NSCLC. 1. The COMPEL study tries to find the value of continuing osimertinib (with the addition of chemotherapy) after progression on osimertinib. The results are, well, compelling! 2/3. We now have updates on the OS benefits of osimertinib + chemotherapy (FLAURA2) and amivantamab + lazertinib (MARIPOSA) compared to osimertinib monotherapy in initial treatment of metastatic disease. 4. NEOADAURA tries to determine if neoadjuvant osimertinib has value, but longer follow-up will be needed to assess this practice.

The 5-year+ follow-up from CARTITUDE-1 has people asking if cilta-cel can cure multiple myeloma? We discuss this data and the broad comparison to the other BCMA-targeting CAR-T product, idi-cel and a recent comparison on plasma cell leukemia. CARTITUDE-1 Long-Term F/U: https://doi.org/10.1200/JCO-25-00760 Cilta-cel & ide-cel in plasma cell leukemia: https://doi.org/10.1182/bloodadvances.2025016966

The potential breakthrough in RNA vaccine technology has been increasingly discussed on social media. This episode looks at one promising study and its early, early results so far. UF GBM study: https://doi.org/10.1016/j.cell.2024.04.003 RNA Treatment Vaccine Review: https://doi.org/10.1002/ctm2.1384

Malignant Hematology Updates: Venetoclax dosing strategies continue to evolve HMA/Ven + IDH1/2 inhibitors: https://doi.org/10.1200/JCO-25-00640 HMA/Ven + revumenib: https://doi.org/10.1200/JCO-25-00914 Venetoclax + CPX-351: https://doi.org/10.1002/ajh.27723 APOLLO: https://doi.org/10.1200/JCO-25-00535 Iland APOLLO editorial: https://doi.org/10.1200/JCO-25-01496 ctDNA assessment vs. PET in Large B-Cell Lymphoma: https://doi.org/10.1200/JCO-25-01534

A new ERBB2 (HER2) targeting TKI is approved for NSCLC. We review the characteristics of the drug and summarize the current landscape in treating HER-mutated advanced NSCLC.

This week's episode discusses the first-in-class agent, dordaviprone and a randomized control trial that demonstrated an oncology pharmacists led to decreased rates of adverse drug reactions (ADRs) in a Hem/Onc clinic. Dordaviprone data: https://doi.org/10.1200/jco.23.01134 Alabassi AK, et al. Role of a designated pharmacist in reducing adverse drug reaction rates and preventing potential medication errors in hematology-oncology: a randomized controlled trial. JCO Oncology Practice: https://doi.org/10.1200/OP-25-00158

More isn't always better. Our Landkmarks of OncoPharm series covers lessons learned from the ProMACE-CytaBOM regimen for NHL. ProMACE-CytaBOM: https://www.annalsofoncology.org/article/S0923-7534(20)31592-1/pdf RCT vs. CHOP (& others): https://www.nejm.org/doi/full/10.1056/NEJM199304083281404

A brief overview of testicular cancer

A few supportive care updates: 1. Skin prophylaxis to prevent severe dermatologic toxicity with Nivo/Ipi. Note* published in JCO Oncology Practice (NOT JAMA Oncol as stated in the episode Link: https://doi.org/10.1200/OP-25-00100 2. Stampede-Metformin and how metformin has some beneficial effects in prostate cancer patients who don't have diabetes Link: https://doi.org/10.1016/S1470-2045(25)00231-1

Two new drug approvals to talk about (after I misplaced my notes!)

Antiandrogen withdrawal is an historically well described phenomenon where prostate cancer patients experience PSA responses AFTER stopping their anti-androgen. But does this happen with today's 2nd generation antiandrogens?

A plethora of recent updates: -Pembrolizumab (perioperative) in head & neck cancer (Keynote-689) -Prostate cancer updates on cabozantinib/atezolizumab (yes, really) and talazoparib -Pirtobrutinib improves PFS in CLL -Zanubrutinib has a new dosage form on the way -Another mitomycin product approved with "reverse thermal properties" -A new regimen for FL of tafasitamab/rituximab/lenalidomide -A comparison of the new ROS1-inhibitor, taltrectenib, compared to other 1st-line treatment options

A recap of notable updates from ASCO 2025 1. Destiny-Breast09 2. BREAKWATER 3. ATOMIC 4. Delphi-304 5. CM 816 OS update 6. C-POST 7. Matterhorn

Our Landmarks of OncoPharm series returns to discuss the CLEOPATRA study, which established docetaxel, trastuzumab, pertuzumab (THP) as a standard first-line regimen for metastatic HER2-amplified breast cancer.

If you've been struggling with how to talk to patients about ivermectin for cancer, then this podcast is for you. 1. Cancer misinformation on social media (Loeb, et al): https://doi.org/10.3322/caac.21857 2. Clinician communication with patients about cancer misinformation (Bylund, et al): https://doi.org/10.1200/OP.22.00526

Discussing recent FDA approvals of penpulimab, avutometenib, defactinib, and telisotuzumab vedotin.

A splashy large study and two small studies suggest IV Mg in pre-hydration fluids can decrease the risk of cisplatin kidney injury. Gupta et al. JAMA Oncol (2025): doi:10.1001/jamaoncol.2025.0756 PRAGMATIC. ESMO Open (2022): https://doi.org/10.1016/j.esmoop.2021.100351 Yamamoto et al. Anticancer Res (2015): https://pubmed.ncbi.nlm.nih.gov/25862878/

This episode summarizes recent updates on: Tumor infiltrating clonal hematopoiesis (TI-CH) and its apparent negative impact on solid tumors (https://www.nejm.org/doi/full/10.1056/NEJMoa2413361) Updated dostarlimab data on MMRd use in rectal cancer and other solid tumors in the neoadjuvant (definitive?!?!) setting (https://www.nejm.org/doi/full/10.1056/NEJMoa2404512) Phase 1 study of 7 + 3 + Venetoclax (https://doi.org/10.1182/blood.2024026700) Zongertinib, a new HER2 TKI (https://www.nejm.org/doi/full/10.1056/NEJMoa2503704)

BRCA revision mutations may explain some of the limited benefit seen in long-term follow-up studies with PARP inhibitors. Bibliography: 1: BRCA reversion mutations predict resistance. https://doi.org/10.1158/2159-8290.CD-18-0715 2: SOLO3 Final OS Data. https://doi.org/10.1200/JCO.24.00933 3: Elucidating acquired PARP inhibitor resistance in advanced prostate cancer. https://doi.org/10.1016/j.ccell.2024.10.015

Recapping HOPA 25 and Portland *Great food (not discussed, the most excellent ETSU dinner at Arden) *COCOON *Pharmacists make everyone's job easier and keep patients out of the ED *A few more tidbits too!