The efficacy and safety profile of the combination of lenvatinib (Lenvima) and pembrolizumab (Keytruda) produced similar efficacy and safety profiles in an East Asian subgroup of patients with advanced renal cell carcinoma (RCC), according to results from the phase 3 CLEAR trial (NCT02811861) presented at the 2022 ASCO Genitourinary Cancers Symposium.¹

The makeup of the East Asian subset consisted of patients from Japan and the Republic of Korea. Their characteristics were generally consistent with the baseline characteristics of the overall patient population from the CLEAR trial. Researchers found that progression-free survival (PFS), similar to the global population, was longer in the combination arm compared with sunitinib alone at a median of 22.1 months compared to 11.1 months, respectively.

The hazard ratio (HR) was comparable in both groups with an HR of 0.38 (95% CI, 13.8-NE) in the East Asian subset compared to the global population HR of 0.39. This consistency extended to the comparison of overall survival (OS) with a HR of 0.71 (95% CI, 0.30-1.71) in the East Asian subset of patients and an HR of 0.66 in the global population.

The phase 3 CLEAR trial had previously reported significant improvements in PFS (HR 0.39; 95% CI, 0.32-0.49; P < .001), OS (HR 0.66; 95%, CI 0.49-0.88; P = .005) and objective response rate (ORR) (odds ratio 4.35; 95% CI, 3.16-5.97) in the global population for patients with advanced RCC in the combination arm. Patients included in the trial had no prior systemic therapy and were randomized 1:1 to receive either 20 mg of lenvatinib orally 4 times a day plus 200 mg of pembrolizumab intravenously every 3 weeks, or 50 mg of sunitinib 4 weeks on and 2 weeks off.

Of the 1609 patients randomized on the study, 75 patients in the combination arm were from East Asia compared to 65 in the sunitinib arm.

ORR was improved in the lenvatinib and pembrolizumab arm in the East Asian subset at 65.3% compared to 49.2% in the monotherapy arm (OR 2.14, 95% CI, 1.07-4.28). Furthermore, duration of response was longer in this subset at 20.3 months compared to 12.9 months. Broken down by complete response (CR) and partial response (PR), the combination therapy remained stronger in this patient subset with a 17.3% CR and 48% PR versus 7.7% CR and 41.5% PR rates in the sunitinib arm.

“This continuation of (results) were similar in both groups, however, dose reductions were higher for this population, which was similar to previous reports,” explained Sun Young Rha, MD, chief of medical oncology at Yonsei University College of Medicine in Seoul, South Korea, in a presentation of data at the ASCO symposium. According to Rha, these were manageable and did not change outcomes of the subset data and was consistent with the rest of the CLEAR trial.

Incidence rates of any grade certain treatment emergent adverse events (TEAEs) greater in the East Asian subset of patients included hand-foot syndrome at 66.7% in the combination arm and 57.8% in the monotherapy arm versus 28.7% and 37.4%, respectively, in the global population.

Proteinuria was higher in the combination group at 56% of the East Asian subset experiencing any grade compared to 29.5% in the global population, while decreased neutrophil was experienced by 26.6% of East Asian patients in the sunitinib group compared to just 11.8% in the global population. Other AEs observed were consistent with the rest of the global population with grade 3 or greater TEAEs occurring in 88% of the patients in the combination arms with discontinuation only rising to 16%.

“This supports the combination of the recommended starting dose of Lenvatinib plus pembrolizumab in appropriate East Asian patients with advanced RCC,” concluded Rha.

_Reference

_{Young Rha, S, Choueiri T, Matveev V, et al. Efficacy and safety of lenvatinib plus pembrolizumab versus sunitinib in the East Asian subset of patients with advanced renal cell carcinoma from the phase 3 CLEAR trial. Presented at: 2022 ASCO Genitourinary Cancers Symposium. Feb. 17-19, 2022. Virtual. Abstract 338}