TY - JOUR
T1 - Second-line lenvatinib in patients with recurrent endometrial cancer
AU - Vergote, Ignace
AU - Powell, Matthew A.
AU - Teneriello, Michael G.
AU - Miller, David S.
AU - Garcia, Agustin A.
AU - Mikheeva, Olga N.
AU - Bidzinski, Mariusz
AU - Cebotaru, Cristina Ligia
AU - Dutcus, Corina E.
AU - Ren, Min
AU - Kadowaki, Tadashi
AU - Funahashi, Yasuhiro
AU - Penson, Richard T.
N1 - Funding Information:
Indication of Research Support for the Study: At the time the research took place, this study was funded by Eisai Inc., Woodcliff Lake, NJ, USA. Funding for the subsequent manuscript and medical writing support was provided by Eisai Inc., and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding Information:
The authors thank the patients, their families, the investigators, and their teams for their contributions to this study. The authors also thank Lea Dutta, PharmD, and Pallavi Sachdev, PhD, of Eisai Inc., and Tamas Pinter, MD, of Aladar Petz Teaching County Hospital, Gyõr, Hungary, for their contributions to the study and development of this manuscript. Tarah M. Connolly, PhD, of Oxford PharmaGenesis Inc., Newtown, PA, USA, provided medical writing assistance, which was funded by Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding Information:
This study was sponsored by Eisai Inc., Woodcliff Lake, NJ, USA. Employees of the study sponsor were involved in the study design; in the collection, analysis, and interpretation of data; and in the writing of the report. The corresponding author (Ignace Vergote) had final responsibility for the decision to submit the paper for publication. Medical writing support was provided by Tarah M. Connolly, Ph.D. of Oxford PharmaGenesis Inc., Newtown, PA, with funding provided by Eisai Inc., Woodcliff Lake, NJ, USA and Eisai Inc., and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Publisher Copyright:
© 2020 The Authors
PY - 2020/3
Y1 - 2020/3
N2 - 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.
AB - 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.
KW - Endometrial cancer
KW - Lenvatinib
KW - Multikinase inhibitor
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U2 - 10.1016/j.ygyno.2019.12.039
DO - 10.1016/j.ygyno.2019.12.039
M3 - Article
C2 - 31955859
AN - SCOPUS:85077924505
SN - 0090-8258
VL - 156
SP - 575
EP - 582
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 3
ER -