Dr Choueiri on the Safety Profile of Adjuvant Belzutifan Plus Pembrolizumab in ccRCC

“When you add belzutifan to pembrolizumab, the 2 AEs that we focus on are anemia and hypoxia. Anemias was [observed] in the majority of patients; it’s a hallmark AE of belzutifan.”

Toni K. Choueiri, MD, the director of the Lank Center for Genitourinary Oncology and the medical director of International Strategic Initiatives at Dana-Farber Cancer Institute, as well as the Jerome and Nancy Kohlberg Professor of Medicine at Harvard Medical School, discussed safety data from the phase 3 LITESPARK-022 trial (NCT05239728) of belzutifan (Welireg) plus pembrolizumab (Keytruda) for the adjuvant treatment of patients with clear cell renal cell carcinoma (ccRCC) after nephrectomy.

Safety data from LITESPARK-022 that were presented during the 2026 Genitourinary Cancers Symposium indicated that 2 adverse effects (AEs) that oncologists should be especially mindful of when using the combination are anemia and hypoxia, Choueiri began. Patients who received the combination (n = 915) experienced any-grade treatment-emergent anemia at a rate of 84.3% compared with 11.7% among patients who received pembrolizumab plus placebo (n = 913). Any-grade treatment-emergent hypoxia occurred at rates of 7.0% and 0.1% in the respective arms.

Choueiri emphasized that anemia is a hallmark AE in patients who are treated with belzutifan. AE management in the investigational arm was mostly addressed via dose reduction and interruption, rather than with erythropoiesis-stimulating agents and blood transfusions, he noted.

Belzutifan has been available for the treatment of patients with RCC since it was approved by the FDA for the treatment of patients with advanced RCC following treatment with a PD-1 or PD-L1 inhibitor and a VEGF TKI in December 2023, so the field is fairly familiar with managing its associated AEs, he concluded.

Disclosures: Choueiri reported holding a leadership position with ASCO; having stock and other ownership Interests with Abalytics Oncology, Bicycle Therapeutics, Curesponse, Faron Pharmaceuticals, Inndura, Osel, Pionyr, Precede Bio, Primium, and Tempest Therapeutics; receiving honorariafrom Alkermes, Analysis Group, Aravive, Arcus Biosciences, ASCO, AstraZeneca, Bayer, Bristol-Myers Squibb, Clinical Care Options, Eisai, EMD Serono, ESMO, Exelixis, Foundation Medicine, Gilead Sciences, Gilead Sciences, GlaxoSmithKline, Harborside Press, HiberCell, Infinity Pharmaceuticals, Ipsen, Janssen Oncology, Kanaph Therapeutics, Lancet Oncology, Lilly, MashupMD, Merck, Michael J. Hennessy Associates, Navinata Health, NCCN, NiKang Therapeutics, Novartis, Peloton Therapeutics, Pfizer, PlatformQ Health, Precede Bio, Prometheus, Roche/Genentech, Sanofi/Aventis, Scholar Rock, Tempest Therapeutics, The New England Journal of Medicine, and UpToDate; holding consulting or advisory roleswith alkermes, Analysis Group, Aravive, Arcus Biosciences, ASCO, AstraZeneca, Bayer, Bicycle Therapeutics, Bristol-Myers Squibb, Caris Life Sciences, Clinical Care Options, Curesponse, Eisai, EMD Serono, ESMO, Exelixis, Foundation Medicine, Gilead Sciences, Gilead Sciences, GlaxoSmithKline, Harborside Press, Infinity Pharmaceuticals, Ipsen, Janssen Oncology, Kanaph Therapeutics, Lancet Oncology, Lilly, Merck, Michael J. Hennessy Associates, Navinata Health, NCCN, Neomorph, NiKang Therapeutics, Novartis, Peloton Therapeutics, Pfizer, PlatformQ Health, Precede Bio, Prometheus, Roche/Genentech, Sanofi/Aventis, Scholar Rock, Tempest Therapeutics, The New England Journal of Medicine, and UpToDate; receiving research fundingfrom Agensys (Inst), Arcus Biosciences (Inst), AstraZeneca (Inst), AVEO (Inst), Bayer (Inst), Bristol-Myers Squibb (Inst), Calithera Biosciences (Inst), Eisai (Inst), Exelixis (Inst), GlaxoSmithKline (Inst), Ipsen (Inst), Merck (Inst), NiKang Therapeutics (Inst), Novartis (Inst), Peloton Therapeutics (Inst), Pfizer (Inst), Roche (Inst), Roche/Genentech (Inst), Seattle Genetics/Astellas (Inst), Takeda (Inst), and TRACON Pharma (Inst); holding patents, royalties, or other Intellectual Propertyfor International Patent Application No. PCT/US2018/058430, entitled “Biomarkers of Clinical Response and Benefit to Immune Checkpoint Inhibitor Therapy (Inst), ctDNA technologies, International Patent Application No. PCT/US2018/12209, entitled “PBRM1 Biomarkers Predictive of Anti-Immune Checkpoint Response (Inst); and receiving travel, accommodations, and/or expenses from Alexion Pharmaceuticals, alligent, Analysis Group, AstraZeneca, Bayer, Bristol-Myers Squibb, Cerulean Pharma, Clinical Care Options, Corvus Pharmaceuticals, Eisai, EMD Serono, ESMO, Exelixis, Foundation Medicine, GlaxoSmithKline, Harborside Press, HERON, Ipsen, Kidney Cancer Association, Lancet Oncology, Lilly, Lpath, Merck, Michael J. Hennessy Associates, Navinata Health, NCCN, Novartis, Peloton Therapeutics, Pfizer, PlatformQ Health, Prometheus, Roche/Genentech, Sanofi/Aventis, The New England Journal of Medicine, and UpToDate.