The US Food and Drug Administration approved belzutifan (Welireg) plus lenvatinib (Lenvima) in adult patients with advanced clear cell renal cell carcinoma following treatment with a PD-1 or PD-L1 inhibitor.
The FDA evaluated the combination therapy's efficacy in the LITESPARK-011 trial, an open-label, randomized, active-controlled trial of 747 patients with advanced clear cell renal cell carcinoma. Eligible patients had locally advanced or metastatic disease that progressed during or following treatment with a PD-1 or PD-L1 inhibitor or within 6 months of completing adjuvant treatment with a PD-1 inhibitor.
Patients were randomly assigned 1:1 to receive belzutifan plus lenvatinib or cabozantinib. Major efficacy outcomes were progression-free survival, assessed by blinded independent central review using RECIST version 1.1, and overall survival. Objective response rate was an additional efficacy outcome.
Median progression-free survival was 15 months with belzutifan plus lenvatinib vs. 11 months with cabozantinib, a statistically significant improvement. Objective response rates were 53% with the combination therapy and 40% with cabozantinib.
In the final analysis, the difference in overall survival was not statistically significant. Median overall survival was 34 months with belzutifan plus lenvatinib vs. 29 months with cabozantinib.
The FDA emphasized that belzutifan prescribing information includes a boxed warning for embryo-fetal toxicity and warnings and precautions for anemia and hypoxia. Warnings and precautions for the belzutifan and lenvatinib combination also include cardiac dysfunction.
Lenvatinib prescribing information includes warnings and precautions 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.
The recommended dosage is lenvatinib 20 mg plus belzutifan 120 mg once daily until disease progression or unacceptable toxicity.
Source: FDA
