Dr Hutson on the Final OS Analysis of the CLEAR Study in Advanced RCC

Thomas Hutson, DO, PharmD, director of the Urologic Oncology Program, cochair, Urologic Cancer Research and Treatment Center, Baylor University Medical Center, professor of medicine, Texas A&M College of Medicine, Texas Oncology, discusses the final prespecified overall survival (OS) analysis of the phase 3 CLEAR study (NCT02811861) in patients with advanced renal cell carcinoma (RCC).

At the 2023 ASCO Annual Meeting, investigators shared the 4-year follow-up of outcomes from the multicenter, open-label, randomized trial evaluating lenvatinib (Lenvima) plus pembrolizumab (Keytruda) vs sunitinib (Sutent) monotherapy in patients with advanced RCC. Results showed that OS was maintained with the combination, further supporting its use in clinical practice. With a final data cutoff of July 31, 2022, investigators found that the median OS, prior to adjustment, for the combination therapy was 53.7 months (95% CI, 48.7-not evaluable [NE]) and 54.3 months (95% CI, 40.9-NE) in the sunitinib arm (HR, 0.79; 0.63-0.99; nominal P-value =.0424). However, when adjusting for subsequent anticancer medications, the final OS was not reached in the lenvatinib plus pembrolizumab arm (95% CI, 40.9-NE) vs 32.0 months (95% CI, 18.7-NE) in the sunitinib arm, with an adjusted HR of 0.55 (95% CI, 0.44-0.69).

Lenvatinib plus pembrolizumab previously demonstrated a statistically significant and clinically meaningful benefit in the primary end point of progression-free survival (PFS), as well as secondary efficacy end points of OS and response rate, Hutson explains. Data from the trial, which were previously been published in the New England Journal of Medicine, served as the basis for the regulatory approval of the combination as frontline therapy for patients with advanced RCC, he says.

Moreover, the data for the secondary efficacy end points were maintained, with a median PFS of 23.9 months and an objective tumor response rate of 71.3% (95% CI, 66.6%-76.0%) with the combination, Hutson continues. Regarding safety, no additional adverse effects were observed with long-term follow-up.