Ignace Vergote1, Matthew A Powell2, Michael G Teneriello3, David S Miller4, Agustin A Garcia5, Olga N Mikheeva6, Mariusz Bidzinski7, Cristina Ligia Cebotaru8, Corina E Dutcus9, Min Ren9, Tadashi Kadowaki10, Yasuhiro Funahashi10, Richard T Penson11. 1. Division of Gynaecological Oncology, University Hospital Leuven, Leuven Cancer Institute, Leuven, Belgium. Electronic address: Ignace.vergote@uzleuven.be. 2. Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA. 3. US Oncology Research, The Woodlands, TX, USA. 4. University of Texas Southwestern Medical Center, Dallas, TX, USA. 5. Louisiana State University, New Orleans, LA, USA. 6. State Healthcare Institution Leningrad Regional Oncology Center, St Petersburg, Russia. 7. Maria Sklodowska-Curie Memorial Institute, Oncology Center, Warsaw, Poland. 8. Department of Radiotherapy I-Medical Oncology, Prof Dr Ion Chircuta Institute of Oncology, Cluj Napoca, Romania. 9. Eisai Inc, Woodcliff Lake, NJ, USA. 10. Eisai Co., Ltd., Tsukuba, Ibaraki, Japan. 11. Division of Hematology and Oncology, Massachusetts General Hospital, Boston, MA, USA.
Abstract
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.
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.
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