PI3K Pathway Hyperglycemia

This episode looks at the combination of PARP inhibitors in combination with androgen receptor pathway inhibitors (ARPi) for untreated advanced prostate cancer. BRCA2 sensitivity > BRCA 1 commentary: https://doi.org/10.1200/JCO.20.02246 Methylphenidate for fatigue in hematologic cancers: https://doi.org/10.1200/JCO-26-00578 Download the Learning Oncology Companion: https://www.kelleycpharmd.com/learning-oncology-companion-oncopharm

ESMO 2026 concluded this past weekend, so this Pod is packed with lots of updates! 1. DeLLphi-305: Maintenance tarlatamab + durvalumab improves OS compared to maintenance durvalumab in extensive stage SCLC. Impressive improvement, but a puzzlingly high rate of dysguesia in the tarlatamab arm that is ~2x what has been reported in tarlatamab monotherapy. 2. Non-ESMO, but related - Lurbinectedin's mono therapy approval for SCLC was was withdrawn following the negative results of the LAGOON trial, which followed the negative results of the ATLANTIS trial. 3. INTerpath-001 was a phase III trial that showed improved recurrence free survival with intismeran autogene + pembrolizumab vs. pembrolizumab in advanced melanoma. This patient-specific mRNA treatment is exciting with more trials planned across solid tumors. 4. Darolutamide may have a role in high-risk prostate cancer following prostatectomy and adjuvant ADT, but longer follow-up (and publication) is likely needed before implementation. 5. VOLGA provides evidence for another sandwich approach in muscle-invasive bladder cancer with durvalumab + enforumab vedotin --> radical cystectomy --> durvalumab (But no more EV). The addition of the CTLA-4 targeting agent tremilimumab appeared to offer no additional benefit. 6. Pemroblizumab's sight agnostic accelerated approval for high Tumor Mutation Burden (TMB) was narrowed from 10+ to 13+ mutations/megabase after a few hundred more patients enrolled and 6 years of follow-up. 7. Adding venetolcax to DA-EPOCH-R in double-hit NHL was associated with excess mortality. Download the Oncology Learning Companion: https://www.kelleycpharmd.com/learning-oncology-companion-oncopharm

This week we take a (brief) stop back in time to the beginning of dostarlimab's journey that has ended (for now) in an accelerated approval for rectal cancer that is mismatch repair-deficient or high in micro-satellite instability (MMRd/h-MSI). Download the Learning Oncology Companion: https://www.kelleycpharmd.com/learning-oncology-companion-oncopharm

This week we discuss the recent RCT of blinatumomab-ponatinib in Ph+ Adult ALL and how this regimen compares to previously publishes uses of Blin-Ponatinib in induction treatment. Link: DOI: 10.1056/NEJMoa2606208 Finally, we discuss two recent expanded indications in bladder cancer (nogapendekin alfa inbakicept + BCG) and colon cancer (atezolizumab with FOLFOX for dMMR colon cancer in the adjuvant setting). Download the Learning Oncology Companion: https://www.kelleycpharmd.com/learning-oncology-companion-oncopharm

Tucatinib gets an expanded FDA approval in the 1st-line treatment of HER2(+) metastatic breast cancer based on the results of HER2-Climb05. Pirtobrutinib also gets FDA approved for initial treatment of CLL/SLL (without 17p deletion). Australia makes a bold decision regarding Nivo/Ipi and Pembrolisumab: https://doi.org/10.1200/JCO-26-01340 Download the Learning Oncology Companion: https://www.kelleycpharmd.com/learning-oncology-companion-oncopharm

This week's pod offers a brief review of FGFR inhibitors for cholangiocarcinoma in repsonse to the FDA approval of the latest one, lirafugratinib. LITESPARK-011 demonstrated improved PFS of lenvantinib + belzutifan vs. cabozantinib in the 2nd-line setting of advanced ccRCC. This led to a recent FDA approval. We look at the toxicity, QOL, and OS data known about this combination regimen. Download the Learning Oncology Companion: https://www.kelleycpharmd.com/learning-oncology-companion-oncopharm

Drugs that inhibit signaling via the PI3K pathway (e.g. alpelisib, capivasertib) can cause hyperglycemia. The mechanism of this ADR as well as the implications of which anti-diabetes medications are used in response is discussed. Review article: https://doi.org/10.1177/15347354211073163 Download the Learning Oncology Companion: https://www.kelleycpharmd.com/learning-oncology-companion-oncopharm

This week's podcast discusses a recent meta-analysis on the benefit of a "neutropenic diet" in patients on treatment for cancer. Link: https://doi.org/10.1200/OP-26-00405 The 2026 World Conference on Lung Cancer just wrapped up. We run through the findings of the most notable trials presented at WCLC. Download the Learning Oncology Companion:https://www.kelleycpharmd.com/learning-oncology-companion-oncopharm

Press Releases are an increasingly common method to learn about new/upcoming data. What can clinicians learn (and what can't we learn) from these? We read through two examples for just this purpose. Example 1: https://www.amgen.com/newsroom/press-releases/2026/09/imdelltra-in-combination-with-imfinzi-demonstrated-landmark-improvement-in-overall-survival-in-first-line-extensive-stage-small-cell-lung-cancer Example 2: https://aptevotherapeutics.gcs-web.com/news-releases/news-release-details/aptevo-reports-93-clinical-benefit-rate-mipletamig-triplet Possible Help with Drug Shortages: https://www.angelsforchange.org Download the Learning Oncology Companion: https://www.kelleycpharmd.com/learning-oncology-companion-oncopharm

PARADIGM is finally published, so we have more details from this study presented at ASH about HMA/Ven vs. Intensive Chemo if fit patients with AML. Daraxonrasib looks like a promising drug for RAS-mutant NSCLC, too. Download the Oncology Learning Companion: https://www.kelleycpharmd.com/learning-oncology-companion-oncopharm