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.

Biostatistics Eisai Inc Nutley New Jersey USA

Clinical Research Eisai Ltd Hatfield UK

Department of Medical Oncology A Policlinico Umberto 1 La Sapienza Università di Roma Rome Italy

Department of Medical Oncology BC Cancer Vancouver Cancer Centre Vancouver British Columbia Canada

Department of Medical Oncology Dana Farber Cancer Institute Boston Massachusetts USA

Department of Medicine Memorial Sloan Kettering Cancer Center New York New York USA

Department of Oncology 1st Faculty of Medicine Charles University and Thomayer University Hospital Prague Czech Republic

Department of Oncology and Internal Medicine University of Ulsan College of Medicine Asan Medical Center Seoul South Korea

Department of Oncology Georges François Leclerc Cancer Centre Dijon France

Department of Oncology Tel Aviv Sourasky Medical Center and School of Medicine Tel Aviv University Tel Aviv Israel

Department of Oncology The Royal Free NHS Trust London UK

Department of Urology and Transplantation Surgery Eva Mayr Stihl Cancer Center Klinikum Stuttgart Stuttgart Germany

Department of Urology Kyushu University Fukuoka Japan

Department of Urology Tokyo Women's Medical University Tokyo Japan

Department of Urology University Hospital of Munich Munich Germany

Division of Hematology Oncology Department of Medicine Samsung Medical Center Sungkyunkwan University School of Medicine Seoul South Korea

Division of Hematology Oncology University of California San Diego La Jolla California USA

Global Clinical Development Merck and Co Inc Rahway New Jersey USA

Interdisciplinary Genitourinary Oncology Clinic for Urology Clinic for Medical Oncology University Hospital Essen Essen Germany

Medical Oncology Vall d'Hebron Institute of Oncology Hospital Universitari Vall d'Hebron Vall d'Hebron Barcelona Hospital Campus Barcelona Spain

University of Lyon Centre Léon Bérard Lyon France

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