Toni Choueiri, MD, reacts to FDA approval of adjuvant belzutifan with pembrolizumab for ccRCC

On June 12, 2026, the FDA approved belzutifan (Welireg) in combination with pembrolizumab (Keytruda) or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) as adjuvant treatment for adult patients with clear cell renal cell carcinoma (ccRCC) at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.¹ In this video, Toni K. Choueiri, MD, offers his perspective on the significance of this approval for patients and the field at large.

Choueiri is the director of the Lank Center for Genitourinary (GU) Oncology at Dana-Farber Cancer Institute in Boston, Massachusetts.

According to Choueiri, this approval represents a significant advance in the adjuvant treatment landscape. He noted that pembrolizumab became the first systemic therapy shown to reduce the risk of recurrence and death in this setting in 2021, ending decades without an effective adjuvant systemic option for kidney cancer. Choueiri emphasized that the addition of belzutifan now builds upon that foundation, offering a further reduction in the risk of recurrence, metastasis, or death.

The approval was based on findings from the phase 3 LITESPARK-022 trial, which demonstrated a statistically significant improvement in disease-free survival with belzutifan plus pembrolizumab compared with pembrolizumab alone (HR, 0.72; 95% CI, 0.59 to 0.87; P = .0003). Choueiri highlighted that the combination reduced the risk of recurrence by approximately 28%, describing the results as an important step forward for patients with high-risk disease following nephrectomy. He also pointed to the convenience of the regimen, which incorporates once-daily oral belzutifan administered for up to 1 year alongside standard pembrolizumab treatment.

Although overall survival data remain immature due to the relatively short follow-up of just over 2 years, Choueiri expressed optimism about the clinical impact of the regimen. He acknowledged that adverse events were more common with the 2-drug combination than with pembrolizumab alone, but noted that the safety profile was manageable overall. Choueiri added that belzutifan has already demonstrated benefit in advanced kidney cancer, making its transition into the adjuvant setting particularly encouraging because it offers the potential to improve outcomes earlier in the disease course.

REFERENCE

1. FDA approves belzutifan with pembrolizumab for adjuvant treatment of renal cell carcinoma. News release. US Food & Drug Administration. June 12, 2026. Accessed June 15, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-belzutifan-pembrolizumab-adjuvant-treatment-renal-cell-carcinoma