ea
Objective response rate 65% 2%
(95% CI) (59%, 71%) (0%, 4%)
Complete response 2% 0%
Partial response 63% 2%
P-valued <0.001
Overall Survivale
Number of deaths (%) 71 (27) 47 (36)
Median OS in months (95% CI) NE (22.1, NE) NE (20.3, NE)
Hazard ratio (95% CI)b 0.73 (0.50, 1.07)
P-valueb 0.10
a Independent radiologic review
b Estimated with Cox proportional hazard model stratified by region (Europe vs North America vs other), age group (≤65 years vs >65 years), and previous VEGF/VEGFR-targeted therapy (0 vs 1)
c Log-rank test stratified by region (Europe vs North America vs other), age group (≤65 years vs >65 years), and previous VEGF/VEGFR-targeted therapy (0 vs 1)
d Cochran-Mantel-Haenszel chi-square test
e NE = Not estimable
Figure 1: Kaplan-Meier Plot of Progression-Free Survival (Study 1)
Figure 1: Kaplan-Meier Plot of Progression-Free Survival (Study 1)
14.2 Renal Cell Carcinoma
A multicenter study (Study 2) randomized 153 patients with advanced or metastatic renal cell carcinoma who have previously received anti-angiogenic therapy 1:1:1 to LENVIMA 18 mg plus everolimus 5 mg, LENVIMA 24 mg monotherapy, or everolimus 10 mg monotherapy. All medications were administered orally once daily. Patients were required to have histological confirmation of clear cell RCC and ECOG Performance Status of 0 or 1. Patients were stratified by hemoglobin level (≤ or > 13 g/dL for males and ≤ or > 11.5 g/dL for females) and corrected serum calcium (≥10 mg/dL vs. <10 mg/dL).
Of the 101 patients randomly allocated to the LENVIMA + everolimus arm and everolimus monotherapy arm, 72% were male, the median age was 60 years, 31% were older than 65 years, 96% were White. Metastases were present in 95% of the patients and unresectable advanced disease was present in 5%. All patients had a baseline ECOG PS of either 0 (54%) or 1 (46%) with similar distribution across the 2 treatment arms. Memorial Sloan Kettering Cancer Center (MSKCC) favorable, intermediate, and poor risk categories were observed respectively, in 24%, 37%, and 39% of patients in the LENVIMA + everolimus arm, and 24%, 38%, and 38% of patients in the everolimus arm.
The major efficacy outcome measure was investigator-assessed PFS eva luated according to RECIST 1.1. Efficacy results from Study 2 are summarized in Table 9 and Figures 2 and 3. The treatment effect of the combination on PFS was supported by a retrospective independent review of radiographs with an observed hazard ratio (HR) of 0.43 (95% CI: 0.24, 0.75) compared with the everolimus arm.
Table 9: Efficacy Results in Renal Cell Carcinoma Per Investigator Assessment (Study 2)
LENVIMA 18 mg + Everolimus 5 mg
(N=51) Everolimus 10 mg
(N=50)
Progression-Free Survival (PFS)a
Number of events, n (%) 26 (51) 37 (74)
Progressive disease 21 (41) 35 (70)
Death 5 (10) 2 (4)
Median PFS in months (95% CI) 14.6 (5.9, 20.1) 5.5 (3.5, 7.1)
Hazard Ratio (95% CI)b
LENVIMA + Everolimus vs Everolimus 0.37 (0.22, 0.62)
-
Overall Survivalc
Number of deaths, n (%) 32 (63) 37 (74)
Median |
