A Randomized Phase II Study of Cabozantinib Versus Weekly Paclitaxel in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer: An NRG Oncology/Gynecologic Oncology Group Study

Gynecol Oncol. 2019 Mar;152(3):548-553. doi: 10.1016/j.ygyno.2018.12.008. Epub 2018 Dec 23.

Abstract

Introduction: Cabozantinib is a receptor tyrosine kinases inhibitor that targets MET (c-MET), VEGF receptor 2 (VEGFR2), RET, AXL, KIT, FLT-3, and TIE-2 and previously showed promising single agent activity in recurrent ovarian cancer.

Methods: This was an open label, 1:1 randomized study of cabozantinib 60 mg orally (PO) daily versus weekly paclitaxel 80 mg/m2 given 3 out of 4 weeks (NCT01716715); 111 patients were enrolled. Eligibility included persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma and at least one but no >3 prior chemotherapy regimens.

Results: Median PFS was similar for both treatment groups and was 5.3 months for cabozantinib and 5.5 months for weekly paclitaxel (HR 1.11 (90% CI 0.77-1.61, p = 0.64)). Secondary analyses of overall survival (OS) and event free survival (EFS) showed that cabozantinib did not perform as well as weekly paclitaxel. Median OS for cabozantinib was 19.4 months and was not reached for weekly paclitaxel (HR 2.27 (90% CI 1.17-4.41, p = 0.04). EFS was also worse in the cabozantinib arm, 3.5 months, compared to weekly paclitaxel at 5.0 months (HR 1.81 (90% CI 1.24-2.63, p = 0.01). Overall response rate (ORR) was less for cabozantinib compared to weekly paclitaxel (7% versus 24.1%). Gastrointestinal toxicities, specifically nausea, diarrhea, and abdominal pain were worse in the cabozantinib arm.

Conclusions: Median PFS was similar for cabozantinib and weekly paclitaxel. However, OS, EFS, and ORR were worse for cabozantinib compared to weekly paclitaxel. Cabozantinib given at this dose and schedule cannot be recommended as a treatment for recurrent ovarian cancer.

Keywords: Anti-vascular; Cabozantinib; Ovarian cancer; Paclitaxel.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Anilides / administration & dosage*
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Carcinoma, Ovarian Epithelial / drug therapy*
  • Drug Administration Schedule
  • Fallopian Tube Neoplasms / drug therapy*
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Ovarian Neoplasms / drug therapy*
  • Paclitaxel / administration & dosage*
  • Peritoneal Neoplasms / drug therapy*
  • Protein Kinase Inhibitors / administration & dosage
  • Pyridines / administration & dosage*

Substances

  • Anilides
  • Antineoplastic Agents, Phytogenic
  • Protein Kinase Inhibitors
  • Pyridines
  • cabozantinib
  • Paclitaxel

Associated data

  • ClinicalTrials.gov/NCT01716715