Updated CLEAR Trial Results: Lenvatinib Plus Pembrolizumab Supported as Standard of Care

At the 2024 American Society of Clinical Oncology Annual Meeting, Viktor Grünwald, MD, PhD, presented a poster featuring updated results of the CLEAR trial that included patterns of progression and subsequent therapy.

The primary analysis and final overall survival analysis of CLEAR found that the use of lenvatinib with pembrolizumab in patients with advanced renal cell carcinoma (aRCC) significantly improved efficacy over sunitinib alone.

A total of 1069 patients with aRCC and a clear cell component were randomly assigned to receive lenvatinib 20 mg by mouth once daily with pembrolizumab 200 mg intravenously every 3 weeks, lenvatinib 18 mg with everolimus 5 mg by mouth once daily, or sunitinib 50 mg by mouth once daily for 4 weeks on and 2 weeks off.

The stratification factors included region and Memorial Sloan Kettering Cancer Center prognostic risk group, which were used to determine hazard ratios (HRs) in the lenvatinib plus pembrolizumab versus sunitinib arms. HR was based on Cox regression models, with treatment as a factor.

The time to progression (TTP) of each organ was defined independently by analyzing lesions within each specific organ, based on independent image review per Response Evaluation Criteria in Solid Tumors v1.1. The Kaplan-Meier method was used to estimate medians and quartiles, while a generalized Brookmeyer and Crowley method was used to estimate CIs of 95%.

The HRs (95% CI) of TTP for lenvatinib plus pembrolizumab versus sunitinib in various organs included 0.40 in bone (0.25-0.63), 0.47 in the central nervous system (0.19-1.19), 0.65 in the kidneys (0.37-1.14), 0.52 in the liver (0.32-0.84), 0.48 in the lungs (0.36-0.62), and 0.63 in the lymph nodes (0.46-0.85).

At the time of overall disease progression, the median sums of the diameters of target lesions were lower in the lenvatinib plus pembrolizumab arm than in the sunitinib arm (29.8 mm vs 42.8 mm). In the lenvatinib plus pembrolizumab arm, 181 patients were treated with subsequent anticancer therapies during survival follow-up (axitinib: 43; cabozantinib: 101).

In the sunitinib arm, 246 patients were given subsequent anticancer therapies (axitinib: 47; cabozantinib: 107). After receiving lenvatinib plus pembrolizumab, the median duration of axitinib as the first anticancer regimen provided (95% CI) was 23.7 months (5.3-not estimable [NE]). After treatment with sunitinib, the median duration was 12.6 months (6.8-NE). The median duration of cabozantinib as the first anticancer regimen (95% CI) after lenvatinib plus pembrolizumab was 13.2 months (8.2-NE). After sunitinib it was 7.1 months (4.1-20.0).

Patients who received lenvatinib plus pembrolizumab experienced later progression across tumors in multiple organs. At overall disease progression, the tumor burden of target lesions was lower in patients who received lenvatinib plus pembrolizumab over sunitinib, although patients in the former arm remained on second-line axitinib or cabozantinib longer than patients in the sunitinib arm.

Lenvatinib plus pembrolizumab continues to be supported as a standard-of-care first-line therapy for patients with aRCC.