Adjuvant Combination for Kidney Cancer Gets FDA’s Blessing

The FDA on Friday approved belzutifan (Welireg) plus pembrolizumab (Keytruda, Keytruda Qlex) as adjuvant therapy for renal cell carcinoma (RCC) with a clear cell component.

Based on results from LITESPARK-022, the combination is indicated for adults at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.

The phase III trial demonstrated that the addition of belzutifan to adjuvant pembrolizumab reduced the risk of disease recurrence or death by 28% versus pembrolizumab and placebo (HR 0.72, 95% CI 0.59-0.87, P=0.0003). At 2 years, disease-free survival reached 80.7% in the belzutifan arm and 73.7% in the placebo arm.

LITESPARK-022 “is the first adjuvant phase III trial in renal cell cancer to show a significant benefit for a combination treatment versus an active immunotherapy comparator,” said Toni Choueiri, MD, of the Dana-Farber Cancer Institute in Boston, in presenting the results at the ASCO Genitourinary Cancers Symposium earlier this year.

“These results, I believe, support the addition of belzutifan to standard of care adjuvant pembrolizumab for patients with clear cell RCC with increased risk of recurrence,” said Choueiri.

With only about 30% of events needed for the final analysis on overall survival — the trial’s key secondary endpoint — the data appeared to favor the belzutifan arm (HR 0.78, 95% CI 0.51-1.19).

Common adverse events (AEs) occurring in at least 20% of patients receiving the combination included fatigue; decreases in hemoglobin or lymphocytes; and increases in alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase.

Serious AEs occurred in 30% of patients who received belzutifan plus pembrolizumab — with pneumonia, hypoxia, pneumonitis, arrhythmia, diarrhea, and acute kidney injury being most frequent — while AEs occurred in 1.1%.

Warnings and precautions in the drug labels include anemia and hypoxia for belzutifan, and immune-mediated AEs, infusion-related reactions, and complications of allogeneic hematopoietic stem cell transplantation for pembrolizumab. Both drugs have warnings about embryo-fetal toxicity.