Key takeaways:

• FDA approved belzutifan plus lenvatinib for adults with advanced renal cell carcinoma after immunotherapy.
• LITESPARK-011 trial data showed 26% improved PFS vs. standard of care.

The FDA approved belzutifan in combination with lenvatinib for adults with advanced renal cell carcinoma with a clear cell component following treatment with a PD-1 or PD-L1 inhibitor.

The combination of belzutifan (Welireg, Merck) plus lenvatinib (Lenvima, Eisai) is indicated for adults with locally advanced or metastatic ccRCC that progressed during or after PD-1/PD-L1 inhibitor therapy, or within 6 months of completing adjuvant PD-1 therapy.

The FDA approved belzutifan in combination with lenvatinib for adults with advanced renal cell carcinoma with a clear cell component following treatment with a PD-1 or PD-L1 inhibitor.

The FDA based its decision on findings from the randomized, phase 3 LITESPARK-011 trial, which demonstrated a 26% improvement in PFS with belzutifan plus lenvatinib compared with cabozantinib (Cabometyx, Exelixis) monotherapy.

In the LITESPARK-011 trial researchers randomly assigned 747 patients (76% men; 87% white) with locally advanced or metastatic ccRCC 1:1 to receive belzutifan plus lenvatinib or cabozantinib. Eligible patients had disease progression during or following treatment with a PD-1 or PD-L1 inhibitor; those who progressed within 6 months of completing adjuvant therapy with a PD-1 inhibitor were also eligible.

PFS and OS served as dual primary outcomes.

Results showed that patients in the combination group had a median PFS of 14.6 months compared with 10.6 months in the cabozantinib group (HR = 0.74; 95% CI, 0.61-0.89).

At time of final analysis, OS data was not statistically significant; however, patients in the combination group did exhibit a statistical benefit (33.7 months vs. 28.6 months; HR = 0.85; 95% CI, 0.7-1.03).

Belzutifan carries a boxed warning for embryo-fetal toxicity, with warnings for anemia and hypoxia. Lenvatinib carries warnings for hypertension, cardiac dysfunction, arterial thromboembolic events, hepatotoxicity, renal failure or impairment, proteinuria, diarrhea, fistula formation and gastrointestinal perforation, QT interval prolongation, hypocalcemia, reversible posterior leukoencephalopathy syndrome, hemorrhagic events, impairment of thyroid stimulating hormone suppression/thyroid dysfunction, impaired wound healing, osteonecrosis of the jaw and embryo-fetal toxicity.

Prescribing information for the combination of these two agents includes warnings and precautions for cardiac dysfunction.

The recommended dose is 120 mg belzutifan plus 20 mg lenvatinib orally once daily until disease progression or unacceptable toxicity.