Bevacizumab plus fosbretabulin in recurrent ovarian cancer: Overall survival and exploratory analyses of a randomized phase II NRG oncology/gynecologic oncology group study

Krishnansu S. Tewari, Michael W. Sill, Robert L. Coleman, Carol Aghajanian, Robert Mannel, Paul A. DiSilvestro, Matthew Powell, Leslie M. Randall, John Farley, Stephen C. Rubin, Bradley J. Monk

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: To explore the relationship between tumor size and response to combined anti-vascular targeted therapy using the anti-angiogenesis inhibitor, bevacizumab, and the tubulin-binding vascular disrupting agent, fosbretabulin. Methods: An exploratory, post-hoc analysis of the randomized phase II trial, Gynecologic Oncology Group-0186I, was performed. One hundred and seven patients with recurrent ovarian carcinoma, treated with up to 3 prior regimens, were randomized to bevacizumab 15 mg/kg body weight with or without intravenous fosbretabulin 60 mg/m2 body surface area every 21 days until progression or unacceptable toxicity. The primary analysis favored the combination (HR 0.69; 95% CI, 0.47–1.00; p =.049) [Monk BJ, et al. J Clin Oncol 2016;34:2279–86]. The Cox proportional hazards model was used to estimate the treatment effect in various subpopulations. Results: With extended follow-up, the median PFS for bevacizumab plus fosbretabulin was 7.6 months as compared to 4.8 months with bevacizumab alone (HR 0.74; 90% CI, 0.54–1.02). Overall survival was similar in the experimental and control arms (25.2 vs 24.4 mos, respectively, HR 0.85; 90% CI, 0.59–1.22; p =.461). Eighty-one patients had measurable disease and median tumor size was 5.7 cm. In the ≤5.7 cm subgroup, the HR for progression or death was 0.77 (90% CI 0.45–1.31). Patients with tumors >5.7 cm (n = 40) had a HR for progression or death of 0.55; 90% CI, 0.32–0.96; p =.075). Conclusions: Although no significant survival benefit was observed, the trend showing a reduced HR for progression or death with increasing tumor size when fosbretabulin is added to bevacizumab compared to bevacizumab alone warrants further study.

Original languageEnglish
Pages (from-to)79-87
Number of pages9
JournalGynecologic oncology
Volume159
Issue number1
DOIs
StatePublished - Oct 2020

Keywords

  • Bevacizumab
  • Fosbretabulin
  • Ovarian cancer
  • Vascular disrupting agent

Fingerprint Dive into the research topics of 'Bevacizumab plus fosbretabulin in recurrent ovarian cancer: Overall survival and exploratory analyses of a randomized phase II NRG oncology/gynecologic oncology group study'. Together they form a unique fingerprint.

Cite this