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

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.

• Authors: 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
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 159 Issue 1 Pg. 79-87 (10 2020) ISSN: 1095-6859 [Electronic] United States
• PMID: 32723679 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Stilbenes
• Bevacizumab
• fosbretabulin

Topics

• Adult
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Bevacizumab (administration & dosage, adverse effects)
• Female
• Follow-Up Studies
• Humans
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy, mortality, pathology)
• Ovarian Neoplasms (drug therapy, mortality, pathology)
• Ovary (drug effects, pathology)
• Progression-Free Survival
• Stilbenes (administration & dosage, adverse effects)
• Time Factors
• Tumor Burden (drug effects)