Dr Choueiri on the Clinical Significance of Adjuvant Belzutifan Plus Pembrolizumab in ccRCC

“There are patients who get pembrolizumab and experience [disease] progression. So, the fact that we now can add a drug that can cut the risk of recurrence by close to 30% is a big deal.”

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 the clinical significance of data from the phase 3 LITESPARK-022 trial (NCT05239728).

LITESPARK-022 evaluated the HIF-2α inhibitor in combination with pembrolizumab (Keytruda) for the adjuvant treatment of patients with clear cell renal cell carcinoma (ccRCC) after nephrectomy. Data presented during the 2026 Genitourinary Cancers Symposium demonstrated that patients who received the combination (n = 921) achieved a median investigator-assessed disease-free survival that was not reached (NR; 95% CI, 36.9-NR) vs NR (95% CI, NR-NR) with pembrolizumab alone (n = 920) in the intention-to-treat population (HR, 0.72; 95% CI, 0.59-0.87; P = .0003).

Choueiri noted that these promising data should mean more options for patients with ccRCC. Although pembrolizumab has an established role in the treatment of patients with RCC, there remain patients who are refractory to the agent, he continued. Adding belzutifan to pembrolizumab in the adjuvant setting has the potential to reduce the risk of disease recurrence by approximately 30%, he added. However, investigators are still eager to see more data with a longer duration of follow-up for the combination, 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.