Upfront lenvatinib plus pembrolizumab improves second progression-free survival (PFS2), when compared with sunitinib, in patients with advanced renal cell carcinoma (RCC), according to updated results from the phase 3 CLEAR study.1

Patients who received lenvatinib plus pembrolizumab also had improved overall survival (OS) after adjustment for subsequent therapies. These findings were presented at IKCS North America 2022.

Previous results from the CLEAR trial (ClinicalTrials.gov identifier: NCT02811861) showed that lenvatinib plus pembrolizumab improved PFS and OS in patients with advanced RCC.2 The median PFS was 23.9 months with the combination and 9.2 months with sunitinib (hazard ratio [HR], 0.39; 95% CI, 0.32-0.49; P <.001). The median OS was not reached in either arm (HR, 0.66; 95% CI, 0.49-0.88; P =.005). 

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For the current analysis, researchers evaluated PFS2 and adjusted OS in patients assigned to receive lenvatinib plus pembrolizumab (n=355) or sunitinib (n=357).1 

The team found that fewer patients in the lenvatinib-pembrolizumab arm received subsequent systemic anticancer therapy than in the sunitinib arm — 117 patients and 206 patients, respectively. 

The median time from randomization to next line of therapy was 12.68 months in the lenvatinib-pembrolizumab arm and 6.62 months in the sunitinib arm. The median duration of first subsequent therapy was 5.16 months and 6.82 months, respectively.

PFS2 was significantly longer in the lenvatinib-pembrolizumab arm than in the sunitinib arm. The median PFS2 was not reached and 28.7 months, respectively (HR, 0.50; 95% CI, 0.39-0.65; P <.0001). The 12-month PFS2 rate was 87.6% in the combination arm and 72.5% in the sunitinib arm. The 24-month PFS2 rates were 72.7% and 54.2%, respectively.

The researchers also found that the OS benefit with lenvatinib-pembrolizumab was more pronounced after accounting for subsequent therapy (HR, 0.54; bootstrap 95% CI, 0.39-0.72).

These results support the use of lenvatinib plus pembrolizumab as a first-line standard care option for patients with advanced RCC, according to the researchers.

Disclosures: This research was supported by Eisai Inc. and Merck Sharp & Dohme LLC. The study authors did not provide disclosures.


1. Voss MH, Powles T, McGregor B, et al. Impact of subsequent therapies in patients with advanced renal cell carcinoma receiving lenvatinib plus pembrolizumab or sunitinib in the CLEAR study. Presented at IKCS North America 2022. November 4-5, 2022. Abstract 36.

2. Motzer R, Alekseev B, Rha SY, et al. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med. 2021;384(14):1289-1300. doi:10.1056/NEJMoa2035716