Dr Choueiri on the FDA Approval of Adjuvant Belzutifan Plus Pembrolizumab in ccRCC

“[This is] a major approval. It’s a major win for patients on top of the pembrolizumab standard of care in adjuvant RCC, a standard of care that we waited 5 decades for.”

Toni 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 significance of the FDA approval of adjuvant belzutifan (Welireg) plus pembrolizumab (Keytruda in clear cell renal cell carcinoma (ccRCC).

In June 2026, the FDA approved belzutifan in combination with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) for the adjuvant treatment of adult patients with ccRCC at intermediate-high or high risk of recurrence following nephrectomy or following nephrectomy and resection of metastatic lesions.

Positive findings from the phase 3 LITESPARK-022 trial (NCT05239728), which supported this approval, represent a significant advancement in the treatment of patients with ccRCC and mark an important milestone in the evolution of adjuvant therapy, Choueiri said. After decades of limited progress in this setting, the approval of pembrolizumab in 2021 established the first widely accepted standard of care for patients with high-risk RCC after surgery, ending a wait of nearly five decades for an effective adjuvant treatment strategy, he added.

Building upon the success of pembrolizumab, investigators launched the international LITESPARK-022 study to evaluate whether the addition of belzutifan to the existing adjuvant standard could further improve patient outcomes, Choueiri said. The trial, which was led by investigators at Dana-Farber Cancer Institute and conducted at sites around the world, examined the combination of belzutifan and pembrolizumab in patients with RCC following definitive surgery, he noted.

At the time of the first interim analysis, the study met its primary end point of disease-free survival, demonstrating that the addition of belzutifan to pembrolizumab provided a meaningful benefit compared with the current standard approach, Choueiri highlighted. Patients who received belzutifan plus pembrolizumab experienced a significant disease-free survival (DFS) benefit compared with those who received placebo plus pembrolizumab (HR, 0.72; 95% CI, 0.59-0.87; P = .0003). The median DFS was not reached in either arm. Overall survival data were not mature at the protocol pre-specified interim analysis.

Overall, the positive results from LITESPARK-022 offer the potential to further improve long-term outcomes for patients with high-risk disease following surgical resection, Choueiri concluded.