As reported in the Journal of Clinical Oncology by Robert J. Motzer, MD, and colleagues, the prespecified final overall analysis of the phase III CLEAR/KEYNOTE-581 trial supported a benefit of lenvatinib/pembrolizumab vs sunitinib in the first-line treatment of advanced renal cell carcinoma.
The trial supported the August 2021 approval of lenvatinib/pembrolizumab in this setting. The combination showed significantly superior progression-free survival on primary analysis and superior overall survival on interim analysis.
Robert J. Motzer, MD
Study Details
In the open-label trial, patients were randomly assigned to receive pembrolizumab at 200 mg every 3 weeks plus lenvatinib at 20 mg once daily in 21-day cycles (n = 355) or sunitinib at 50 mg once daily for 4 weeks on/2 weeks off (n = 357).
At data cutoff in July 2022, median follow-up was 49.8 months (interquartile range [IQR] = 41.4–53.1 months) in the lenvatinib/pembrolizumab group and 49.4 months (IQR = 41.6–52.8 months) in the sunitinib group. Death occurred in 149 patients in the combination group vs 159 patients in the sunitinib group (hazard ratio = 0.79, 95% confidence interval [CI] = 0.63–0.99, nominal P = .0424).
Median overall survival was 53.7 months (95% CI = 48.7 months to not estimable) in the lenvatinib/pembrolizumab group vs 54.3 months (95% CI = 40.9 months to not estimable) in the sunitinib group; rates at 36 months were 66.4% (95% CI = 61.1%–71.2%) vs 60.2% (95% CI = 54.6%–65.2%). Among patients who completed 35 cycles of pembrolizumab and continued lenvatinib monotherapy (approximately one-third of the treatment group), overall survival at 36 months was 94.2% (95% CI = 88.2%–97.2%).
Subsequent anticancer therapy was received by 51.0% of patients in the lenvatinib/pembrolizumab group vs 68.9% of the sunitinib group, including PD-1/PD-L1 inhibitors in 15.8% vs 54.6%, respectively. In an analysis adjusting for subsequent anticancer therapy use, the adjusted overall survival hazard ratio for lenvatinib/pembrolizumab vs sunitinib was 0.55 (95% CI = 0.44–0.69).
The investigators concluded, “Lenvatinib plus pembrolizumab achieved consistent, durable benefit with a manageable safety profile in treatment-naive patients with advanced renal cell carcinoma.”
Dr. Motzer, of Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Eisai Inc, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc. For full disclosures of the study authors, visit ascopubs.org.
