In the CLEAR trial, lenvatinib plus pembrolizumab met study endpoints of superiority vs sunitinib in the first-line treatment of patients with advanced renal cell carcinoma. We report the efficacy and safety results of the East Asian subset (ie, patients in Japan and the Republic of Korea) from the CLEAR trial. Of 1069 patients randomly assigned to receive either lenvatinib plus pembrolizumab, lenvatinib plus everolimus or sunitinib, 213 (20.0%) were from East Asia. Baseline characteristics of patients in the East Asian subset were generally comparable with those of the global trial population. In the East Asian subset, progression-free survival was considerably longer with lenvatinib plus pembrolizumab vs sunitinib (median 22.1 vs 11.1 months; HR 0.38; 95% CI: 0.23-0.62). The HR for overall survival comparing lenvatinib plus pembrolizumab vs sunitinib was 0.71; 95% CI: 0.30-1.71. The objective response rate was higher with lenvatinib plus pembrolizumab vs sunitinib (65.3% vs 49.2%; odds ratio 2.14; 95% CI: 1.07-4.28). Dose reductions due to treatment-emergent adverse events (TEAEs) commonly associated with tyrosine kinase inhibitors occurred more frequently than in the global population. Hand-foot syndrome was the most frequent any-grade TEAE with lenvatinib plus pembrolizumab (66.7%) and sunitinib (57.8%), a higher incidence compared to the global population (28.7% and 37.4%, respectively). The most common grade 3 to 5 TEAEs were hypertension with lenvatinib plus pembrolizumab (20%) and decreased platelet count with sunitinib (21.9%). Efficacy and safety for patients in the East Asian subset were generally similar to those of the global population, except as noted.

Biostatistics Oncology Business Group Eisai Inc Nutley New Jersey USA

Clinical Research Merck and Co Inc Rahway New Jersey USA

Clinical Research Oncology Business Group Eisai Inc Nutley New Jersey USA

Department of Internal Medicine and Medical Therapy University of Pavia and Medical Oncology Unit Fondazione IRCCS Policlinico San Matteo Pavia Italy

Department of Medical Oncology Dana Farber Cancer Institute Boston Massachusetts USA

Department of Medical Oncology Hospital Universitario Ramón y Cajal Madrid Spain

Department of Medical Oncology Macquarie University Sydney New South Wales Australia

Department of Medical Oncology Yonsei Cancer Center Yonsei University Health System Seoul South Korea

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

Department of Oncology Prevoljskiy Region Medical Centre Novgorod Russia

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

Department of Urology Federal State Budgetary Institution N N Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation Moscow Russia

Department of Urology Kyushu University Fukuoka Japan

Department of Urology Seoul St Mary's Hospital Seoul South Korea

Department of Urology Tokyo Women's Medical University Hospital Tokyo Japan

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

Division of Medical Oncology Department of Medicine Odette Cancer Centre Sunnybrook Health Sciences Centre Toronto Ontario Canada

Zobrazit více v PubMed

World Cancer Research Fund International. Kidney cancer statistics. https://www.wcrf.org/cancer-trends/kidney-cancer-statistics. Accessed September 26, 2022

International Agency for Research on Cancer, World Health Organization. Globocan 2020: Cancer Today. https://gco.iarc.fr/today/online-analysis-table?v=2020&mode=cancer&mode_population=continents&population=900&populations=900&key=asr&sex=0&cancer=39&type=0&statistic=5&prevalence=0&population_group=0&ages_group%5B%5D=0&ages_group%5B%5D=17&group_cancer=1&include_nmsc=0&include_nmsc_other=1. Accessed September 26, 2022

Kanesvaran R, Porta C, Wong A, et al. Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with renal cell carcinoma. ESMO Open. 2021;6:100304.

Arabsalmani M, Mohammadian-Hafshejani A, Ghoncheh M, et al. Incidence and mortality of kidney cancers, and human development index in Asia; a matter of concern. J Nephropathol. 2017;6:30-42.

LENVIMA® (Lenvatinib) Capsules [Prescribing Information]. Nutley: Eisai Inc.; 2022.

Kisplyx 4 mg and 10 mg Hard Capsules [Summary of Product Characteristics]. Frankfurt am Main, Germany: Eisai GmbH; 2022.

Eisai Co., Ltd., Tokyo, Japan, Merck & Co., Inc., Rahway, NJ. Lenvima® (lenvatinib) plus Keytruda® (pembrolizumab) approved in Japan for patients with unresectable, advanced or recurrent endometrial carcinoma that progressed after cancer chemotherapy. First approval in Japan for the Lenvima plus Keytruda combination [press release]. December 24, 2021. https://www.eisai.com/news/2021/news2021103.html. Accessed August 17, 2022

Yun-mi K. Keytruda+lenvima wins indication for renal cell carcinoma, endometrial carcinoma. Korea Biomedical Review. Seoul, Korea: The Korean Doctor's Weekly Co., Ltd; 2022. http://www.koreabiomed.com/news/articleView.html?idxno=12934. Accessed August 17, 2022.

Motzer R, Alekseev B, Rha SY, et al. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med. 2021;384:1289-1300.

KEYTRUDA® (Pembrolizumab) Injection [Prescribing Information]. Rahway: Merck Sharp & Dohme LLC; 2022.

Motzer RJ, Escudier B, Bukowski R, et al. Prognostic factors for survival in 1059 patients treated with sunitinib for metastatic renal cell carcinoma. Br J Cancer. 2013;108:2470-2477.

Guo J, Jin J, Oya M, et al. Safety of pazopanib and sunitinib in treatment-naive patients with metastatic renal cell carcinoma: Asian versus non-Asian subgroup analysis of the COMPARZ trial. J Hematol Oncol. 2018;11:69.

Liu X, Fiocco M, Swen JJ, Guchelaar HJ. Assessment of ethnic differences in sunitinib outcome between Caucasian and Asian patients with metastatic renal cell carcinoma: a meta-analysis. Acta Oncol. 2017;56:582-589.

Sorich MJ, Rowland A, Kichenadasse G, Woodman RJ, Mangoni AA. Risk factors of proteinuria in renal cell carcinoma patients treated with VEGF inhibitors: a secondary analysis of pooled clinical trial data. Br J Cancer. 2016;114:1313-1317.

Ohtsu A, Shah MA, Van Cutsem E, et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011;29:3968-3976.

Sawaki A, Ohashi Y, Omuro Y, et al. Efficacy of trastuzumab in Japanese patients with HER2-positive advanced gastric or gastroesophageal junction cancer: a subgroup analysis of the Trastuzumab for Gastric Cancer (ToGA) study. Gastric Cancer. 2012;15:313-322.

Choueiri TK, Eto M, Kopyltsov E, et al. Phase III CLEAR trial in advanced renal cell carcinoma (aRCC): outcomes in subgroups and toxicity update [abstract]. Ann Oncol. 2021;32(Suppl 5):S683-S685.

Eto M, Takagi T, Kimura G, et al. Lenvatinib plus pembrolizumab versus sunitinib for advanced renal cell carcinoma: Japanese patients from the CLEAR study. Cancer Med. 2023;12(6):6902-6912. doi:10.1002/cam1004.5483

Motzer RJ, Porta C, Eto M, et al. Phase 3 trial of lenvatinib (LEN) plus pembrolizumab (PEMBRO) or everolimus (EVE) versus sunitinib (SUN) monotherapy as a first-line treatment for patients (pts) with advanced renal cell carcinoma (RCC) (CLEAR study) [abstract]. J Clin Oncol. 2021;39(Suppl 6):269.

Kiyota N, Schlumberger M, Muro K, et al. Subgroup analysis of Japanese patients in a phase 3 study of lenvatinib in radioiodine-refractory differentiated thyroid cancer. Cancer Sci. 2015;106:1714-1721.

Zhang A, Gurney H. Racial disparity in metastatic renal cell cancer: the pharmaco-anthropology of sunitinib. Asia Pac J Clin Oncol. 2014;10:197-199.

Ang QY, Alba DL, Upadhyay V, et al. The East Asian gut microbiome is distinct from colocalized white subjects and connected to metabolic health. Elife. 2021;10:10.

Zobrazit více v PubMed

ClinicalTrials.gov
NCT02811861