DISCUSSION
toxicities, endometrial cancer, proteinuria, RCC
ENDOMETRIAL CANCER, SOLID TUMORS, RCC
Our subset analysis of Japanese patients randomized to receive lenvatinib plus pembrolizumab or sunitinib in the CLEAR study demonstrated clinical benefit consistent with the observations in the overall CLEAR study population.Notably, median dose intensity was lower in Japanese patients (lenvatinib, 9.47 mg/day; sunitinib, 25.45 mg/day) than in the overall population (lenvatinib, 13.93 mg/day; sunitinib, 41.59 mg/day). These differences, which may be due to the careful management of specific TKI‐related toxicities that occurred more frequently in Japanese patients than in the overall population (discussed in detail below), should be considered when comparing efficacy and safety among the Japanese and overall CLEAR study populations. Importantly, although lower median dose intensity was observed for Japanese patients from the CLEAR trial, a previous phase 1 study of lenvatinib in Japanese patients with advanced solid tumors showed that lenvatinib was tolerated up to 24 mg once daily with no dose‐limiting toxicities reported at this dose.The overall safety profile of lenvatinib plus pembrolizumab in this study was manageable and generally consistent with the known safety profile of the combination.Although safety profiles were generally similar among Japanese and overall populations of patients who received lenvatinib plus pembrolizumab, some important differences in the frequency of specific TEAEs among Japanese patients and the overall CLEAR study population emerged.A higher incidence of treatment‐emergent proteinuria of any grade was also observed in the phase 3 Study 309/KEYNOTE‐775 in Japanese patients with advanced endometrial cancer who received lenvatinib plus pembrolizumab (63.5%)Recently, a randomized phase 2 trial (Study 218) comparing two starting doses of lenvatinib (14 mg vs. 18 mg; both in combination with everolimus) in patients with advanced RCC, showed that the lower starting dose of lenvatinib (in combination with everolimus) was not noninferior to the higher starting dose, based on a test of ORR at week 24 in the 14 mg versus the 18 mg arm.