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.
International journal of cancer. 2024 Dec 30 [Epub ahead of print]
Viktor Grünwald, Rana R McKay, Tomas Buchler, Masatoshi Eto, Se Hoon Park, Toshio Takagi, Sylvie Zanetta, Daniel Keizman, Cristina Suárez, Sylvie Négrier, Jae Lyun Lee, Daniele Santini, Jens Bedke, Michael Staehler, Christian Kollmannsberger, Toni K Choueiri, Robert J Motzer, Joseph E Burgents, Ran Xie, Chinyere E Okpara, Thomas Powles
Interdisciplinary Genitourinary Oncology, Clinic for Urology, Clinic for Medical Oncology, University Hospital Essen, Essen, Germany., Division of Hematology-Oncology, University of California San Diego, La Jolla, California, USA., Department of Oncology, First Faculty of Medicine, Charles University and Thomayer University Hospital, Prague, Czech Republic., Department of Urology, Kyushu University, Fukuoka, Japan., Division of Hematology/Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea., Department of Urology, Tokyo Women's Medical University, Tokyo, Japan., 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., Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain., University of Lyon, Centre Léon Bérard, Lyon, France., Department of Oncology and Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea., Department of Medical Oncology A, Policlinico Umberto 1, La Sapienza Università di Roma, Rome, Italy., Department of Urology and Transplantation Surgery, Eva Mayr-Stihl Cancer Center, Klinikum Stuttgart, Stuttgart, Germany., Department of Urology, University Hospital of Munich, Munich, Germany., 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., Global Clinical Development, Merck & Co., Inc., Rahway, New Jersey, USA., Biostatistics, Eisai Inc., Nutley, New Jersey, USA., Clinical Research, Eisai Ltd., Hatfield, UK., Department of Oncology, The Royal Free NHS Trust, London, UK.