Lenvatinib/Pembrolizumab Boosts Outcomes For Next Line Therapy in Advanced Renal Cell Carcinoma


Frontline treatment with lenvatinib plus pembrolizumab decreased risk of disease progression or death by 50% compared with sunitinib in advanced renal cell carcinoma.

Results from a prespecified analysis of the phase 3 CLEAR trial (NCT02811861) found that lenvatinib (Lenvima) plus pembrolizumab (Keytruda) improved progression on next line of therapy (PFS2) outcomes compared with sunitinib (Sutent) in patients with advanced renal cell carcinoma (RCC), according to findings presented at the 2022 ASCO Annual Meeting.

The median PFS2 was not reached (95% CI, not estimable [NE]-NE) for the 355 patients in the lenvatinib plus pembrolizumab cohort compared with 28.7 months (95% CI, 23.0-NE) among the 357 patients in the sunitinib cohort. The risk of second progression was reduced by 50% (HR, 0.50; 95% CI, 0.39-0.65).

At the 24-month mark, PFS2 rate was 72.7% (95% CI, 67.3%-77.4%) and 54.2% (95% CI, 48.4%-59.6%) in the investigative combination therapy and sunitinib arms, respectively. At 36 months, PFS2 rate was 61.9% (95% CI, 53.7%-69.0%) and 42.9% (95% CI, 32.8%-52.5%) in the lenvatinib/pembrolizumab arm and sunitinib arm, respectively.

“These findings remained consistent after accounting for subsequent therapies, as evidenced by PFS2 and adjusted overall survival,” the authors wrote in a poster of the data. “These results further support the use of lenvatinib plus pembrolizumab as a standard-of-care first-line treatments for patients with [advanced] RCC.”

A total of 117 patients in the lenvatinib plus pembrolizumab cohort and 206 patients in the sunitinib cohort went on to receive another therapy. Median time to next-line therapy was 12.2 months (range, 1.45-37.36) and 6.4 months (range, 0.39-28.52) in the lenvatinib/pembrolizumab and sunitinib groups, respectively.

The most common next-line of therapy was anti-VEGF treatment, mainly cabozantinib (Cabometyx) which was received by 33.0% of patients in the lenvatinib/pembrolizumab cohort and 57.7% in the sunitinib group. Other therapies included checkpoint inhibition (30.4% and 33.6%, respectively), MTOR inhibition (8.2% and 43.1%), CTLA-4 inhibition (1.7% and 5%), and other (1.7% and 5%).

A PFS2 benefit was also seen with lenvatinib plus pembrolizumab over sunitinib in patients with favorable-risk disease (HR, 0.47; 95% CI, 0.26-0.87), intermediate-risk disease (HR, 0.53; 95% CI, 0.39-0.71), and poor-risk disease (HR, 0.42; 95% CI, 0.20-0.88) defined by Memorial Sloan Cancer Center risk criteria.

Similarly, when defined by International Metastatic Renal Cell Carcinoma Database Conortium risk groups, median PFS2 was not reached for the favorable, intermediate, or poor-risk groups for those on lenvatinib plus pembrolizumab, and was 34.7 months (95% CI, 28.7-NE), 23.0 months (95% CI, 17.7-NE), and 10.2 months (95% CI, 4.2-12.2), in the sunitinib groups, respectively.

Median duration of first subsequent treatment was 5.2 months (range, 0.10-31.23) for the lenvatinib plus pembrolizumab cohort and 6.8 months (range, 0.03-30.72) in the sunitinib cohort.

To be eligible for the trial, patients had to have a histologically or cytologically confirmed diagnosis of RCC with clear-cell components and documented evidence of advanced disease. Patients could not have undergone prior systemic therapy have one or more measurable lesion per RECIST 1.1 criteria and a Karnofsky performance score of 70 or higher.


Voss MH, Powels T, McGregor BA, et al. Impact of subsequent therapies in patients (pts) with advanced renal cell carcinoma (aRCC) receiving lenvatinib plus pembrolizumab (LEN + PEMBRO) or sunitinib (SUN) in the CLEAR study. J Clin Oncol. 2022;40(suppl 16):4514. doi:10.1200/JCO.2022.40.16_suppl.4514

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