OncoPharm

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!

FDA expands approvals for durvalumab (bladder cancer) and Lutetium-177 vipivotide tetraxetan (pre-taxane in metastatic prostate cancer). Portland has places.

A Foundations of OncoPharm episode on Topotecan. (Originally to be released week of 3/27)

We discuss reduced dose apixaban for months 6+ of treating cancer-associated VTE (API-CAT) and the impact (or lack thereof) of pausing BTK-inhibitors around vaccination (IMPROVE)

The updated Keynote 811 OS results convert an accelerated approval for pembrolizumab to a regular approval, albeit restricted by PD-L1 CPS status of 1 or higher.

There is a decent track record with mixed results for cryotherapy to prevent taxane-induced peripheral neuropathy. The POLAR trial adds to this body of evidence that trends in favor of cryotherapy. Compression therapy is another alternative. Both are studied in POLAR. POLAR: doi:10.1001/jamaoncol.2025.0001

Ten of the top herb-chemotherapy interactions. About Herbs website: https://www.mskcc.org/cancer-care/diagnosis-treatment/symptom-management/integrative-medicine/herbs/search Also, search 'About Herbs' in your app store.

Two recent publications suggest modifications to standard subcutaneous daratumumab pre-meds is safe...and saves time! Padmaraju et al experience from Chicago Med Center: https://doi.org/10.1093/oncolo/oyae158 Vazirnia et al experience from Mayo Clinic: https://doi.org/10.1200/OP.23.00470 We end summarizing some emerging evidence about the need, or lack thereof, for pre-paclitaxel H2RAs.

We take a deep look at the recently published, and guideline changing, AMPLIFY trial of fixed-duration acalabrutinib in CLL. Link: DOI: 10.1056/NEJMoa2409804

Morbidity & Mortality (M & M) are common case conferences to learn from unfortunate cases to improve care in the future. This episode looks at two recently published case reports. 1. Fatal tumor lysis syndrome following a lack of venetoclax ramp-up in AML: https://www.jhoponline.com/issue-archive/2024-issues/december-2024-vol-14-no-6/rapid-onset-of-fatal-tumor-lysis-syndrome-in-a-patient-with-acute-myeloid-leukemia-receiving-azacitidine-and-venetoclax-without-a-ramp-up-schedule-a-case-report 2. CD4+ T-cell lymphoma harboring a CAR integration into TP53: https://www.nejm.org/doi/full/10.1056/NEJMoa2411507

Dipping into the archives (technology issues with new computer) to re-release the Foundations of OncoPharm episode on rituximab. Where did that 375 mg/m2 dose come from anyway?

FDA approves two new treatment regimens: 1. Acalabrutinib + BR for untreated mantle cell lymphoma patients deemed ineligible for autologous HSCT 2. Sotorasib + panitumumab for KRAS-G12C mutated metastatic colorectal cancer (after chemotherapy, including oxaliplatin and irinotecan)

Datopotamab deruxtecan, a newly approved agent for breast cancer, is discussed.

HOPA Pharmacy Outcomes & Practice-Based Collaboration Survey: https://www.surveymonkey.com/r/MXNVRBR Dexamethasone Dosing Intensity in Multiple Myeloma: https://doi.org/10.1182/blood.2024025939 Talquetamab + Teclistamab: https://doi.org/10.1182/blood.2024025939 postMONARCH: https://doi.org/10.1200/JCO-24-02086

We discuss recent approvals of ensartinib and nivolumab-hyaluronidase as well as new front-line option for BRAV-V600E mutated metastatic colorectal cancer.

Weighing the Pros & Cons of the accelerated approval pathway as it relates to oncology. An updated draft guidance document from FDA regarding this pathway and some compelling data regarding the public's perceived value of newly approved drugs for cancer. Article: Preferences for speed of access versus certainty of the survival benefit of new cancer drugs: a discrete choice experiment. Forest R, et al. Lancet Oncology 2024. Link: https://doi.org/10.1016/S1470-2045(24)00596-5

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/

Reflections from vacation on 1) How similar the chef training experience on The Bear mirrors some pharmacy residency training and 2) being a resource to family/friends with oncology questions.

Running through recent updates on epcoritamab, adagrasib + cetuximab for colorectal cancer, endometrial cancer, adjuvant dabrafenib/trametinib melanoma follow-up data, and topical capsaicin for delayed CINV. Also, a brief travelogue on my inaugural trip to ATOPP (advanced topics for oncology pharmacy professionals) Summit.

The MARIPOSA study suggests there may be a new preferred first line regimen (amivantamab + lazertinib) for metastatic EGFR-mutated NSCLC, as this regimen improved PFS compared to osimertinib.

An experimental regimen for DLBCL piques my interest. Venetoclax ibrutinib Prednisone Obinutuzumab Revlimid (lenalidomide) Link: https://www.nejm.org/doi/pdf/10.1056/NEJMoa2401532

A new drug is approved for MDS. While some will likely benefit from this new agent, the more enticing news is that inhibiting telomerase may be an attractive target for many malignancies.

Lots and lots of updates from the past weekend's ASCO annual meeting. 1. ADRIATIC (consolidation durvalumab in limited stage SCLC) 2. NADINA (neoadjuvant Nivo/Ipi in stage III melanoma) 3. *NICHE-2 (neoadjuvant Nivo/Ipi in dMMR colon cancer) 4. CheckMate 8HW (Nivo/Ipi in dMMR metastatic colon cancer) 5. TRANSMET (liver transplantation in colon cancer with liver mets) 6. Eposec (FLOT > CROSS in adenocarcinoma of the esophagus) 7. LAURA (forever osimertinib in stage III EGFR-mutated NSCLC post-chemoRT) 8. CROWN (5 year update of lorlatinib in ALK+ NSCLC) 9. Destiny Breast-06 (T-DXd vs. chemo in HER-2 low and "ultra" low MBC who haven't received chemo in metastatic setting) 10. ASC4FIRST (Asciminib first line in CML. Funny title, amirite?)

ASCO & ONS (along with pharmacist representation) released updated safety standards for preparing, administering, and monitoring chemotherapy. Look for a calendar invitation to review your site's policies soon. Link: https://doi.org/10.1200/OP.24.00216