Second-line lenvatinib in patients with recurrent endometrial cancer

Gynecol Oncol. 2020 Mar;156(3):575-582. doi: 10.1016/j.ygyno.2019.12.039. Epub 2020 Jan 17.

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.

Keywords: Endometrial cancer; Lenvatinib; Multikinase inhibitor.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / blood
  • Endometrial Neoplasms / blood
  • Endometrial Neoplasms / drug therapy*
  • Endometrial Neoplasms / pathology
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Recurrence, Local / blood
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / pathology
  • Phenylurea Compounds / adverse effects
  • Phenylurea Compounds / therapeutic use*
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use
  • Quinolines / adverse effects
  • Quinolines / therapeutic use*
  • Survival Rate

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Quinolines
  • lenvatinib