Subgroups analysis from the CLEAR trial of lenvatinib plus pembrolizumab showed efficacy results were consistent between East Asian patients and the overall study population.
Data from the CLEAR trial (NCT02811861) that were presented at the 2022 Genitourinary Cancers Symposium indicated a benefit to therapy with lenvatinib (Lenvima) plus pembrolizumab (Keytruda) in an East Asian subgroup of patients with advanced renal cell carcinoma (RCC) like that seen in the overall population.
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. Investigators found that progression-free survival (PFS), like 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 (HR, 0.38; 95% CI, 13.8-NE), respectively. The hazard ratio was comparable with that derived from the global population (HR 0.39; 95% CI, 0.32-0.49; P <.001).
Efficacy consistency extended to the comparison of overall survival (OS), with an HR of 0.71 (95% CI, 0.30-1.71) in the East Asian subset of patients and an HR of 0.66 (95%, CI, 0.49-0.88) in the global population.
The phase 3 CLEAR trial had previously reported significant improvements with the combination in terms of PFS, OS, and objective response rate (ORR) in the global population of patients with advanced RCC. 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 daily plus 200 mg of pembrolizumab intravenously every 3 weeks, or 50 mg of sunitinib for 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.
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. J Clin Oncol. 2022;40(suppl 6):338. doi:10.1200/JCO.2022.40.6_suppl.338