As reported in The Lancet Oncology by Toni K. Choueiri, MD, and colleagues, extended follow-up of the phase III CLEAR trial has shown maintained progression-free and overall survival benefits with first-line lenvatinib plus pembrolizumab vs sunitinib in patients with advanced clear cell renal cell carcinoma.
The primary analysis of the trial supported the August 2021 approval of the combination in this setting. At primary analysis, hazard ratios (HRs) for lenvatinib/pembrolizumab vs sunitinib were 0.39 (P < .001) for progression-free survival, the primary endpoint, and 0.66 (P = .005) for overall survival.
Study Details
In the open-label trial, patients were randomly assigned 1:1:1 between October 2016 and July 2019 to receive either:
- Lenvatinib at 20 mg per day in 21-day cycles plus pembrolizumab at 200 mg every 21 days (n = 355)
- Lenvatinib plus everolimus (not included in analysis; n = 357)
- Sunitinib at 50 mg per day for 4 weeks on and 2 weeks off (n = 357).
The current analysis includes 7 months of additional follow-up in the lenvatinib/pembrolizumab group vs the sunitinib group in a protocol-specified updated overall survival analysis in the intention-to-treat population.
Key Findings
Median follow-up for progression-free survival was 27.8 months (interquartile range [IQR] = 20.3–33.8 months) in the lenvatinib/pembrolizumab group and 19.4 months (IQR = 5.5–32.5 months) in the sunitinib group. Median progression-free survival was 23.3 months (95% confidence interval [CI] = 20.8–27.7 months) in the lenvatinib/pembrolizumab group vs 9.2 months (95% CI = 6.0–11.0 months) in the sunitinib group (HR = 0.42, 95% CI = 0.34–0.52). Rates at 12, 18, and 24 months were 70.6% vs 38.4%, 57.2% vs 31.2%, and 48.6% vs 22.6%, respectively.
Efficacy benefits of lenvatinib plus pembrolizumab over sunitinib were durable and clinically meaningful with extended follow-up. These results support the use of lenvatinib plus pembrolizumab as a first-line therapy for patients with advanced renal cell carcinoma.— Toni K. Choueiri, MD, and colleagues
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Subsequent anticancer treatment was received by 37% of patients in the lenvatinib/pembrolizumab group vs 62% of those in the sunitinib group. Median time from random assignment to subsequent treatment was 14.8 months vs 7.1 months.
Median follow-up for overall survival was 33.7 months (IQR = 27.4–36.9 months) in the lenvatinib/pembrolizumab group and 33.4 months (IQR = 26.7–36.8 months) in the sunitinib group. Median overall survival was not reached (95% CI = 41.5 months to not estimable) in the lenvatinib/pembrolizumab group vs not reached (95% CI = 38.4 months to not estimable) in the sunitinib group (HR = 0.72, 95% CI = 0.55–0.93). Rates at 12, 18, 24, and 36 months were 91.4% vs 80.2%, 86.9% vs 73.8%, 80.2% vs 69.7%, and 65.5% vs 61.8%, respectively.
The investigators concluded, “Efficacy benefits of lenvatinib plus pembrolizumab over sunitinib were durable and clinically meaningful with extended follow-up. These results support the use of lenvatinib plus pembrolizumab as a first-line therapy for patients with advanced renal cell carcinoma.”
Dr. Choueiri, of the Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Eisai and Merck Sharp & Dohme. For full disclosures of the study authors, visit thelancet.com.
