Second-line lenvatinib in patients with recurrent endometrial cancer.

Objective: This study assessed the efficacy of lenvatinib, a multitargeted tyrosine kinase inhibitor, as second-line therapy in patients with unresectable endometrial cancer. The primary end point was the objective response rate (ORR) as assessed by independent radiologic review (IRR). Secondary end points included median progression-free survival (PFS), overall survival (OS), and clinical benefit rate. Exploratory end points examined the association of baseline levels of plasma biomarkers (50 circulating cytokine and/or angiogenic factors measured by immunoassays) with efficacy outcomes.
Methods: An international, open-label, single-arm, multicenter, phase 2 trial was conducted. Eligible patients had histologically confirmed unresectable endometrial cancer that relapsed after 1 prior systemic platinum-based chemotherapy. Patients received once-daily oral lenvatinib 24 mg in a 28-day dosing cycle.
Results: There were 133 patients in the study. By IRR, 19 patients had a confirmed objective response for an ORR of 14.3% (95% CI: 8.8-21.4). Durable stable disease (≥23 weeks) was observed in 31 patients (23.3%) and the clinical benefit rate was 37.6% (95% CI: 29.3-46.4). Median PFS was 5.6 months (95% CI: 3.7-6.3), and median OS was 10.6 months (95% CI: 8.9-14.9). The most common (any grade) treatment-related adverse events were fatigue/asthenia (48%), hypertension (49%), nausea/vomiting (32%), decreased appetite (32%), and diarrhea (31%). Lower baseline levels of angiopoietin-2 were associated with longer PFS, OS, and a higher ORR.
Conclusions: Patients with recurrent endometrial cancer treated with second-line lenvatinib experienced modest antitumor activity and treatment was generally well tolerated, with a safety profile consistent with previous studies.
Competing Interests: Declaration of competing interest Ignace Vergote: Personal fees from Advaxis, Inc., Eisai, Inc., F. Hoffman-La Roche Ltd., Millennium Pharmaceuticals, Oncoinvent AS, Sotio, and MSD Belgium; personal fees and nonfinancial support from Roche NV, Genmab, PharmaMar, Clovis Oncology, AstraZeneca NV, Tesaro, and Immunogen Inc. Grants from Amgen, Roche, and Stichting tegen Kanker. Other (contracted research) support from Oncoinvent AS, Genmab. Nonfinancial support (accommodations and travel) from Takeda Oncology. All outside the submitted work. Matthew A. Powell: Personal fees from Tesaro, Merck, Roche/Genentech, Clovis Oncology, AstraZeneca, Johnson & Johnson, Eisai. All outside the submitted work. Michael G. Teneriello: Nothing to disclose. David S. Miller: Consultancy with Tesaro, Eisai, Incyte, Karyopharm, Genentech, and Merck. Grants (grants pending) from nVision Medical, Advenchen, Forty Seven, Merck, and Syros. Agustin A. Garcia: Advisory board participation for GlaxoSmithKline. Grants and personal fees (regional advisory board) from Eisai, during the conduct of the study. Olga N. Mikheeva: Nothing to disclose. Mariusz Bidzinski: Nothing to disclose. Cristina Ligia Cebotaru: Advisory board participation for Boehringer-Ingelheim, Novartis, Pfizer, Merck. Lecture fees from AstraZeneca, BMS, Bayer, Ipsen, and Astellas. Travel grants from Alvogen, Merck, and Boehringer-Ingelheim. Educational grants from AstraZeneca. Corina E. Dutcus: Employee of Eisai during the conduct of the study. Min Ren: Employee of Eisai during the conduct of the study. Tadashi Kadowaki: Personal fees from Eisai Co., Ltd., during the conduct of the study. Yasuhiro Funahashi: Employee of Eisai during the conduct of the study, and a related patent (WO2002032872A1) issued. Richard T. Penson: Grants and personal fees from Eisai Inc., and from Merck & Co., Inc., during the conduct of the study.
(Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)