Characterization of Responses to Lenvatinib plus Pembrolizumab in Patients with Advanced Renal Cell Carcinoma at the Final Prespecified Survival Analysis of the Phase 3 CLEAR Study

Abstract

In the phase 3 CLEAR trial, lenvatinib plus pembrolizumab (L + P) showed superior efficacy versus sunitinib in treatment-naïve patients with advanced renal cell carcinoma (aRCC). The combination treatment was associated with a robust objective response rate of 71%. Here we report tumor responses for patients in the L + P arm in CLEAR, with median follow-up of ∼4 yr at the final prespecified overall survival (OS) analysis. Tumor responses were assessed by independent review using Response Evaluation Criteria in Solid Tumors v1.1. Patients with a complete response (CR; n = 65), partial response (PR) with maximum tumor shrinkage ≥75% (near-CR; n = 59), or PR with maximum tumor shrinkage <75% (other PR; n = 129), were characterized in terms of their baseline characteristics. The median duration of response was 43.7 mo (95% confidence interval [CI] 39.2-not estimable) for the CR group, 30.5 mo (95% CI 22.4-not estimable) for the near-CR group, and 17.2 mo (95% CI 12.5-21.4) for the other PR group. The 36-mo OS rates were consistently high in the CR (97%), near-CR (86%), and other PR (62%) groups. Robust objective response rates were observed across International Metastatic RCC Database Consortium favorable-risk (69%, 95% CI 60-78%), intermediate-risk (73%, 95% CI 67-79%), and poor-risk (70%, 95% CI 54-85%) subgroups. The robust response to L + P supports this combination as a standard-of-care first-line treatment for patients with aRCC. PATIENT SUMMARY: The CLEAR trial enrolled patients with advanced kidney cancer who had not previously received any treatment for their cancer. Here we report results for tumor shrinkage observed in the group that received lenvatinib plus pembrolizumab combination treatment during the trial. Shrinkage of target tumors with this combination was long-lasting and was observed in patients irrespective of their disease severity. This trial is registered on ClinicalTrials.gov as NCT02811861.

Keywords: Lenvatinib; Lenvatinib plus pembrolizumab; Pembrolizumab; Renal cell carcinoma.

Fig. 1 –

(A) Change in size of target lesions from baseline to postbaseline nadir by independent imaging review per RECIST v1.1 for responders per IMDC risk subgroups, (B) characterization of patients with a confirmed complete or near-complete response, and (C) OS by BOR category, all in the lenvatinib plus pembrolizumab arm of CLEAR. The IMDC prognostic group at baseline is based on total risk score from 6 prognostic factors at baseline: KPS, hemoglobin, corrected serum calcium, neutrophils, platelets, and time from first renal cell cancer diagnosis to randomization. IMDC risk groups were not a stratification factor and relevant data were derived programmatically. Figure 1A includes patients (m) with both baseline and ≥1 postbaseline target lesion assessment. In Figure 1B, arrows at the end of response lines indicate an ongoing response. The number of deaths in the responder subcategories were as follows: CR, 8 patients; near-CR, 15 patients; other PR, 65 patients. BOR, best overall response; CI, confidence interval; CR, complete response; IMDC, International Metastatic Renal Cell Carcinoma Database Consortium; KPS, Karnofsky Performance Status; NE, not estimable; NR, not reached; OS, overall survival; PR, partial response; RECIST v1.1, Response Evaluation Criteria In Solid Tumors version 1.1.

Fig. 1 –

(A) Change in size of target lesions from baseline to postbaseline nadir by independent imaging review per RECIST v1.1 for responders per IMDC risk subgroups, (B) characterization of patients with a confirmed complete or near-complete response, and (C) OS by BOR category, all in the lenvatinib plus pembrolizumab arm of CLEAR. The IMDC prognostic group at baseline is based on total risk score from 6 prognostic factors at baseline: KPS, hemoglobin, corrected serum calcium, neutrophils, platelets, and time from first renal cell cancer diagnosis to randomization. IMDC risk groups were not a stratification factor and relevant data were derived programmatically. Figure 1A includes patients (m) with both baseline and ≥1 postbaseline target lesion assessment. In Figure 1B, arrows at the end of response lines indicate an ongoing response. The number of deaths in the responder subcategories were as follows: CR, 8 patients; near-CR, 15 patients; other PR, 65 patients. BOR, best overall response; CI, confidence interval; CR, complete response; IMDC, International Metastatic Renal Cell Carcinoma Database Consortium; KPS, Karnofsky Performance Status; NE, not estimable; NR, not reached; OS, overall survival; PR, partial response; RECIST v1.1, Response Evaluation Criteria In Solid Tumors version 1.1.