Promise Shown With Lenvatinib Plus Pembrolizumab as SOC in Front-line Advanced RCC


Decreased risk of disease progression or death on second-line therapy with the combination of lenvatinib and pembrolizumab vs sunitinib in the CLEAR clinical trial.

The combination of lenvatinib (Lenvima) and pembrolizumab (Keytruda) demonstrated a 50% reduction in risk of progression or death on second-line therapy vs sunitinib (Sutent) for patients with advanced renal cell carcinoma (RCC), according to findings from the phase 3 CLEAR trial (NCT02811861) presented at the 2022 American Society of Clinical Oncology Annual Meeting.1

Researchers analyzed progression-free survival on next-line therapy (PFS2) in patients (n = 355) who received lenvatinib plus pembrolizumab, and compared it to patients prescribed sunitinib (n = 357) in the randomized, open-label CLEAR trial. Median PFS2 was not reached for the lenvatinib plus pembrolizumab cohort (95% CI, not evaluable), and was 28.7 months in the sunitinib cohort (95% CI, 23.0 months-not evaluable).

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 dual 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 OS,” the researchers wrote.

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 thelenvatinib/pembrolizumab and sunitinib groups, respectively.

The most common next-line of therapy was anti-VEGF treatment, mainly cabozantinib (Cabometyx) (33.0% of patients in the lenvatinib/pembrolizumab cohort and 57.7% in the sunitinib group), followed by 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%).

PFS2 was also seen with lenvatinib plus pembrolizumab over sunitinib in patients with favorable (not reached vs 24.7 months, 95% CI, 28.7-not evaluable), intermediate (not reached vs 23.6 months 95% CI, 19.9-NE), and poor (not reached vs 10.2 months, 95% CI, 6.6-NE) MSKCC risk groups.

Similarly, in the IMDC risk groups, median PFS2 was not reached for the favorable, intermediate, or poor-risk groups for those on lenvatinib plus pembrolizumab, though it 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 for the lenvatinib plus pembrolizumab cohort (range, 0.10-31.23) and 6.8 months in the sunitinib cohort (range, 0.03-30.72).

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 Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and a Karnofsky performance score of 70 or higher.

“These results further support the use of lenvatinib plus pembrolizumab as a standard-of-care first-line treatments for patients with [advanced] RCC,” the authors wrote.

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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