Characterization and Management of Adverse Reactions in Patients With Advanced Endometrial Cancer Receiving Lenvatinib Plus Pembrolizumab (Interpretation In Rus.
Authors:   Gynecologic Oncology Department, European Institute of Oncology IRCCS, Colombo Nicoletta ,   Department of Medicine and Surgery, University of Milan-Bicocca, Lorusso Domenica ,   Division of Gynecologic Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS and Catholic University of Sacred Heart, Monk Bradley J. ,   HonorHealth Research Institute, University of Arizona, Creighton Universit, Hasegawa Kosei ,   Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Nogueira-Rodrigues Angélica ,   Universidade Federal de Minas Gerais (UFMG), Brazilian Group of Gynecologic Oncology (EVA), Grupo Oncoclínicas, DOM Oncologia, Zale Melissa ,   Clinical Safety & Risk Management Late-Stage Oncology – Gynecologic Cancers, Merck & Co., Inc., Okpara Chinyere E. ,   Clinical Research, Eisai Ltd., Barresi Gianmaria ,   Merck & Co., Inc.,, McKenzie Jodi ,   Oncology Business Group, Eisai Inc., Nutley, Makker Vicky ,   Department of Medicine, Memorial Sloan Kettering Cancer Center; Weill Cornell Medical Center
Published: June 2024

Background. Lenvatinib plus pembrolizumab significantly improved efficacy compared with chemotherapy in patients with advanced endometrial cancer (aEC) regardless of microsatellite instability status or histologic subtype, who had disease progression following prior platinum-based therapy, in Study-309/KEYNOTE-775. The safety profile of the combination was generally consistent with that of each monotherapy drug and of the combination in patients with endometrial cancer and other solid tumors. Given the medical complexity of patients with aEC, this paper aims to characterize key adverse reactions (ARs) of the combination treatment and review management strategies, providing a guide for AR management to maximize anticancer benefits and minimize treatment discontinuation. Materials and methods. In Study-309/KEYNOTE-775, patients received lenvatinib (20 mg orally once daily) plus pembrolizumab (200 mg intravenously every 3 weeks) or chemotherapy (doxorubicin or paclitaxel). The incidence and median time to the first onset of ARs, dose modifications, and concomitant medications are described. Key ARs characterized include hypothyroidism, hypertension, fatigue, diarrhea, musculoskeletal disorders, nausea, decreased appetite, vomiting, stomatitis, weight decreased, proteinuria, and palmar-plantar erythrodysesthesia syndrome. Results. As expected, the most common any-grade key ARs included: hypothyroidism, hypertension, fatigue, diarrhea, and musculoskeletal disorders. Grades 3-4 key ARs with incidence ≥10% included: hypertension, fatigue, and weight decreased. Key ARs first occurred within approximately 3 months of treatment initiation. AR management strategies consistent with the prescribing information and the study protocol are discussed. Conclusion. Successful AR management strategies for lenvatinib plus pembrolizumab include education of the patient and entire treatment team, preventative measures and close monitoring, and judicious use of dose modifications and concomitant medications.