Gynecologic Oncology Department, European Institute of Oncology IRCCS, Milan, Italy.
Department of Medicine and Surgery, University of Milan-Bicocca, Italy.
Oncologist. 2024 Jan 5;29(1):25-35. doi: 10.1093/oncolo/oyad201.
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.
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.
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.
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.
CLINICALTRIALS.GOV ID: NCT03517449.
仑伐替尼联合帕博利珠单抗在既往铂类化疗后进展的晚期子宫内膜癌（aEC）患者中，与化疗相比，无论微卫星不稳定状态或组织学亚型如何，均显著改善了疗效。在 Study-309/KEYNOTE-775 研究中，对于接受过先前铂类治疗后疾病进展的晚期子宫内膜癌患者，仑伐替尼联合帕博利珠单抗与化疗相比显著改善了疗效。联合用药的安全性与每种单药治疗药物以及子宫内膜癌和其他实体瘤患者的联合用药的安全性一致。鉴于 aEC 患者的医疗复杂性，本文旨在描述该联合治疗方案的关键不良反应（AR），并复习管理策略，为最大限度地发挥抗癌益处和减少治疗中断提供 AR 管理指南。
在 Study-309/KEYNOTE-775 中，患者接受仑伐替尼（每天口服 20mg）联合帕博利珠单抗（每 3 周静脉注射 200mg）或化疗（多柔比星或紫杉醇）。描述了不良反应的发生率和首次出现时间、剂量调整和伴随用药。描述的关键不良反应包括甲状腺功能减退症、高血压、疲劳、腹泻、肌肉骨骼疾病、恶心、食欲下降、呕吐、口腔炎、体重减轻、蛋白尿和掌跖感觉丧失综合征。
与预期一致，最常见的任何等级的关键不良反应包括：甲状腺功能减退症、高血压、疲劳、腹泻和肌肉骨骼疾病。发生率≥10%的 3-4 级关键不良反应包括：高血压、疲劳和体重减轻。关键不良反应在开始治疗后约 3 个月内首次出现。讨论了符合药物说明书和研究方案的不良反应管理策略。
仑伐替尼联合帕博利珠单抗的成功不良反应管理策略包括对患者和整个治疗团队进行教育、预防措施和密切监测，以及明智地使用剂量调整和伴随用药。
NCT03517449。
