Oncopharmpod

We discuss the newly approved CD20-CD3 T-cell engager for subcutaneous (SC) administration to treat DLBLC after 2 or more lines of therapy.

A recent paper serves as a good prompt to discuss trimodality treatment for muscle-invasive bladder cancer and the data supporting its use. Zlotta et al: https://doi.org/10.1016/S1470-2045(23)00170-5

Today's Pod discusses... 1) A large trial comparing 4 different CLL treatments GAIA-CLL13: https://www.nejm.org/doi/full/10.1056/NEJMoa2213093 2)Adding Cabozantinib + Nivo/Ipo vs. Nivo/Ipi in intermediate/poor risk mRCC COSMIC-313: https://www.nejm.org/doi/full/10.1056/NEJMoa2212851 3) A potential future biomarker for predicting response to PD-(L)1 targeted therapies Functional PD-1/PD-L1 Engagement: https://pubmed.ncbi.nlm.nih.gov/?term=36821809

Talking 3rd-line treatment of metastatic colon cancer. Tipiracil-trifluridine + bevacizuamb vs. tipiracil-trifluridine alone. And a bit on the theory of "bevacizumab beyond progression." SUNLIGHT: https://www.nejm.org/doi/full/10.1056/NEJMoa2214963

Quizartinib vs. Placebo(?) + Chemo in newly diagnosed AML. We add a bit of context about quizartinib's history leading up to this study preview possible role in therapy if approved in the future. Link: https://doi.org/10.1016/S0140-6736(23)00464-6

We take a peak at an intriguing study (n = 29) that gave some metastatic RCC patients receiving nivolumab + ipilimumab a supplement of a bacterium (n = 19) and a control group. We discuss what to look for in the future studies that are likely to follow with similar methods.

The Landmarks of OncoPharm series returns to discuss NSABP's B18 story of neoadjuvant vs. adjuvant AC in stages I & II breast cancer from 1998. B18: https://pubmed.ncbi.nlm.nih.gov/?term=36989610 Flashback Flashforeward: https://pubmed.ncbi.nlm.nih.gov/?term=36989608

Lots of updates: Olanzapine increases weight gain, QOL in some advanced cancer: https://pubmed.ncbi.nlm.nih.gov/?term=36977285 Chemotherapy Toxicity - When Less is More: https://www.nejm.org/doi/full/10.1056/NEJMcibr1202395 Pembro + Chemo improves PFS > chemo alone in advanced endometrial cancer: https://www.nejm.org/doi/full/10.1056/NEJMoa2302312 Enfortumab vedotin + pembrolizumab gets an accelerated approval for cisplatin-ineligible patients with urothelial carcinoma. Safety signals seen.

With new Pod this week, we're re-releasing the 2nd episode from way back in 2017 that provides a historical overview of how the use of EGFR TKIs changed from their use in all NSLCLC to only with activating mutations.

Not that you always need extended gram positive coverage, but if you did... As is often the case with this Pod, this is mostly providing historical context. Link: https://doi.org/10.1086/500139

Prompted by a recent JCO review article (link below), it seemed like a good idea to discuss risks of ovarian dysfunction in women of childbearing potential, what drugs have the highest risk, and fertility preservation techniques. Review article: https://pubmed.ncbi.nlm.nih.gov/?term=29620997 Cyclophosphamide dose equivalent calculator: https://www.oncofertilityrisk.com/CED.html

We review a clever study looking at neoadjvuant & adjuvant pembrolizumab vs. only adjuvant pembrolizumab in melanoma. Link: 10.1056/NEJMoa2211437 We also discuss some updates on abemaciclib and osimertinib

Landkarmks of OncoPharm: Dose-Adjusted EPOCH (+ R) This episode focuses on the pharmacodynamic rationale for the protocol and delivery, not so much the details of the literature supporting its use. Wilson et al 2002, Blood: https://doi.org/10.1182/blood.V99.8.2685

Cannabinoids appear to impact immune system function, so could cannabis use blunt the effect of immune checkpoint inhibitors? I don't know, brah. Maybe? Review: https://pubmed.ncbi.nlm.nih.gov/?term=35749680 Cannabis associated with poorer ORR: https://doi.org/10.1634/theoncologist.2018-0383 Cannabis associated with poorer TTP & OS: https://doi.org/10.3390/cancers12092447

Ide-Cel vs. "standard" treatment in relapsed/refreactory multiple myeloma study - the KarMMa-3 trial - is discussed. Link: https://www.nejm.org/doi/full/10.1056/NEJMoa2213614

CodeBreak200: docetaxel vs. sotorasib in 2nd-line metastatic NSCLC (KRAS-G12C). A new safety signal emerges. https://doi.org/10.1016/S0140-6736(23)00221-0 A new survival prediction model for elderly patients with AML not receiving intensive therapy. https://doi.org/10.1002/cncr.34609

First - despite what you'll hear - it is pirTobrutinib, not pirobrutinib. Second - lots of great information on the current state of targeted therapies in adjuvant NSCLC and on two exciting new drugs: elacestrant and pirtobrutinib.

Tucatinib's FDA-approval (with trastuzumab) for HER2 amplified metastatic colorectal cancer launches a new era of targeted therapy in colorectal cancer. Targeting HER2 (amplified in ~3-5% of advanced colorectal cancers) in colorectal cancer will likely evolve over the coming years, so a brief history on how it has evolved so far may be helpful.

The Landmarks in OncoPharm series returns to discuss adjuvant interferon in melanoma. ECOG 1684: https://pubmed.ncbi.nlm.nih.gov/?term=36649675 Commentary on E1684: https://ascopubs.org/doi/abs/10.1200/JCO.22.02354

Broad, big picture overview of breast cancer and its treatment. Ambitious. Do not recommend listening at 1.5x