Final Overall Survival of a Randomized Trial of Bevacizumab for Primary Treatment of Ovarian Cancer.

Abstract

PURPOSE:

We report the final, protocol-specified analysis of overall survival (OS) in GOG-0218, a phase III, randomized trial of bevacizumab in women with newly diagnosed ovarian, fallopian tube, or primary peritoneal carcinoma.

METHODS:

A total of 1,873 women with incompletely resected stage III to IV disease were randomly assigned 1:1:1 to six 21-day cycles of intravenous carboplatin (area under the concentration v time curve 6) and paclitaxel (175 mg/m2) versus chemotherapy plus concurrent bevacizumab (15 mg/kg, cycles 2 to 6) versus chemotherapy plus concurrent and maintenance bevacizumab (cycles 2 to 22). Inclusion criteria included a Gynecologic Oncology Group performance status of 0 to 2 and no history of clinically significant vascular events or evidence of intestinal obstruction. OS was analyzed in the intention-to-treat population. A total of 1,195 serum and/or tumor specimens were sequenced for BRCA1/2 and damaging mutations in homologous recombination repair (HRR) genes. Intratumoral microvessel density was studied using CD31 immunohistochemistry.

RESULTS:

Median follow-up was 102.9 months. Relative to control (n = 625), for patients receiving bevacizumab-concurrent (n = 625), the hazard ratio (HR) of death was 1.06 (95% CI, 0.94 to 1.20); for bevacizumab-concurrent plus maintenance (n = 623), the HR was 0.96 (95% CI, 0.85 to 1.09). Disease-specific survival was not improved in any arm. No survival advantage was observed after censoring patients who received bevacizumab at crossover or as second line. Median OS for stage IV bevacizumab-concurrent plus maintenance was 42.8 v 32.6 months for stage IV control (HR, 0.75; 95% CI, 0.59 to 0.95). Relative to wild type, the HR for death for BRCA1/2 mutated carcinomas was 0.62 (95% CI, 0.52 to 0.73), and for non-BRCA1/2 HRR, the HR was 0.65 (95% CI, 0.51 to 0.85). BRCA1/2, HRR, and CD31 were not predictive of bevacizumab activity.

CONCLUSION:

No survival differences were observed for patients who received bevacizumab compared with chemotherapy alone. Testing for BRCA1/2 mutations and homologous recombination deficiency is essential.

• Authors: Krishnansu S Tewari, Robert A Burger, Danielle Enserro, Barbara M Norquist, Elizabeth M Swisher, Mark F Brady, Michael A Bookman, Gini F Fleming, Helen Huang, Howard D Homesley, Jeffrey M Fowler, Benjamin E Greer, Matthew Boente, Sharon X Liang, Chenglin Ye, Carlos Bais, Leslie M Randall, John K Chan, J Stuart Ferriss, Robert L Coleman, Carol Aghajanian, Thomas J Herzog, Philip J DiSaia, Larry J Copeland, Robert S Mannel, Michael J Birrer, Bradley J Monk
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 37 Issue 26 Pg. 2317-2328 (09 10 2019) ISSN: 1527-7755 [Electronic] United States
• PMID: 31216226 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Bevacizumab
• Carboplatin
• Paclitaxel

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Bevacizumab (administration & dosage, adverse effects)
• Carboplatin (administration & dosage, adverse effects)
• Carcinoma, Ovarian Epithelial (drug therapy, mortality)
• Double-Blind Method
• Female
• Humans
• Kaplan-Meier Estimate
• Middle Aged
• Ovarian Neoplasms (drug therapy, mortality)
• Paclitaxel (administration & dosage, adverse effects)
• Young Adult