Clinical outcomes by baseline metastases in patients with renal cell carcinoma treated with lenvatinib plus pembrolizumab versus sunitinib: Post hoc analysis of the CLEAR trial

Abstract

Lenvatinib plus pembrolizumab significantly improved efficacy versus sunitinib in treatment of advanced renal cell carcinoma (aRCC) in the phase 3 CLEAR study. We report results of an exploratory post hoc analysis of tumor response data based on baseline metastatic characteristics of patients who received lenvatinib plus pembrolizumab versus sunitinib, at the final overall survival analysis time point of CLEAR (cutoff: July 31, 2022). Treatment-naïve adults with aRCC were randomized to: lenvatinib (20 mg PO QD in 21-day cycles) plus pembrolizumab (n = 355; 200 mg IV Q3W); lenvatinib plus everolimus (not reported here); or sunitinib (n = 357; 50 mg PO QD; 4 weeks on/2 weeks off). The most common (lenvatinib plus pembrolizumab; sunitinib, respectively) metastatic site was lung (71.0%; 63.9%), followed by lymph node (45.6%; 43.7%), bone (22.5%; 24.9%), and liver (17.7%; 19.6%). Across treatment arms, ≥65% had two or more metastatic organs/sites involved, >80% of patients had nontarget lesions, and ~45% had baseline sums of diameters of target lesions ≥60 mm. Lenvatinib plus pembrolizumab demonstrated greater progression-free survival, objective response rate, and duration of response versus sunitinib across evaluable subgroups regardless of site or size of baseline metastasis or number of metastatic sites at baseline. Overall survival generally trended to favor lenvatinib plus pembrolizumab versus sunitinib; and tumor shrinkage was greater across sites (lung, lymph node, liver, and bone) for patients in the lenvatinib-plus-pembrolizumab arm versus the sunitinib arm. These results further support lenvatinib plus pembrolizumab as a standard-of-care in patients with aRCC regardless of site or size of baseline metastasis or the number of metastatic sites.

Keywords: lenvatinib; lenvatinib plus pembrolizumab; pembrolizumab; renal cell carcinoma.

FIGURE 1

Progression‐free survival by independent imaging review per RECIST v1.1 (A), and overall survival (B) in subgroups of the lenvatinib plus pembrolizumab versus sunitinib arms. Data for all subgroups in (A) were derived based on information obtained from the independent imaging review. Median PFS and OS were estimated with Kaplan–Meier method, and 95% CI was constructed with a generalized Brookmeyer and Crowley method. Stratification factors were geographic region (Region 1: Western Europe and North America, Region 2: Rest of the world) and MSKCC prognostic groups (favorable, intermediate, and poor risk) in the interactive voice/web response system. If a stratification factor was within its own subgroup, this factor was excluded from stratified analysis. ^aPatients who died or had progressive disease (for PFS); patients who died (for OS); ^bHazard ratio was based on a Cox proportional hazards model including treatment group as a factor; Efron method was used for ties. Stratification factors were geographic region (Region 1: Western Europe and North America, Region 2: Rest of the world) and MSKCC prognostic groups (favorable, intermediate, and poor risk) in the interactive voice/web response system; ^cThe number of patients with baseline brain metastasis was very low. The data should be interpreted cautiously, considering this. CI, confidence interval; DOR, duration of response; HR, hazard ratio; L + P, lenvatinib plus pembrolizumab; MSKCC, Memorial Sloan Kettering Cancer Center; NE, not estimable; ORR, objective response rate; OS, overall survival; PFS, progression‐free survival; RECIST v1.1, Response Evaluation Criteria in Solid Tumors version v1.1; S, sunitinib.

FIGURE 2

Tumor response and duration of response by independent imaging review per RECIST v1.1 in subgroups of the lenvatinib plus pembrolizumab versus sunitinib arms. ^aThe number of patients with baseline brain metastasis was very low. The data should be interpreted cautiously, considering this; ^bOdds ratios were calculated using the Cochran–Mantel–Haenszel method, stratified by interactive voice/web response system stratification factors; ^cMedian DOR is for all responders. Medians were estimated with Kaplan–Meier product‐limit method and 95% CIs were constructed with a generalized Brookmeyer and Crowley method. Derivation of data was based on information obtained from the independent imaging review. Stratification factors were geographic region (Region 1: Western Europe and North America, Region 2: Rest of the world) and MSKCC prognostic groups (favorable, intermediate, and poor risk) in the interactive voice/web response system. If a stratification factor was within its own subgroup, this factor was excluded from stratified analysis. Arrows indicate 95% CI values that fall outside the scale of the graph. CI, confidence interval; DOR, duration of response; L + P, lenvatinib plus pembrolizumab; MSKCC, Memorial Sloan Kettering Cancer Center; NE, not estimable; ORR, objective response rate; RECIST v1.1, Response Evaluation Criteria in Solid Tumors version v1.1; S, sunitinib.

FIGURE 3

Percentage change in the sum of diameters of target lesions in the lung (A), lymph nodes (B), liver (C), and bone (D) from baseline to postbaseline nadir. These figures include patients (m) with baseline and at least 1 postbaseline target lesion assessment in the respective organ per independent imaging review.