Final overall survival of a randomized trial of bevacizumab for primary treatment of ovarian cancer

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. ColemanCarol Aghajanian, Thomas J. Herzog, Philip J. DiSaia, Larry J. Copeland, Robert S. Mannel, Michael J. Birrer, Bradley J. Monk

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2317-2328
Number of pages12
JournalJournal of Clinical Oncology
Volume37
Issue number26
DOIs
StatePublished - Sep 10 2019
Externally publishedYes

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Ovarian Neoplasms
Survival
Recombinational DNA Repair
Therapeutics
Maintenance
Drug Therapy
Carcinoma
Safety Management
Bevacizumab
Mutation
Fallopian Tubes
Intestinal Obstruction
Homologous Recombination
Carboplatin
Survival Analysis
Paclitaxel
Microvessels
Blood Vessels
Immunohistochemistry
Serum

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Tewari, K. S., Burger, R. A., Enserro, D., Norquist, B. M., Swisher, E. M., Brady, M. F., ... Monk, B. J. (2019). Final overall survival of a randomized trial of bevacizumab for primary treatment of ovarian cancer. Journal of Clinical Oncology, 37(26), 2317-2328. https://doi.org/10.1200/JCO.19.01009

Final overall survival of a randomized trial of bevacizumab for primary treatment of ovarian cancer. / Tewari, Krishnansu S.; Burger, Robert A.; Enserro, Danielle; Norquist, Barbara M.; Swisher, Elizabeth M.; Brady, Mark F.; Bookman, Michael A.; Fleming, Gini F.; Huang, Helen; Homesley, Howard D.; Fowler, Jeffrey M.; Greer, Benjamin E.; Boente, Matthew; Liang, Sharon X.; Ye, Chenglin; Bais, Carlos; Randall, Leslie M.; Chan, John K.; Stuart Ferriss, J.; Coleman, Robert L.; Aghajanian, Carol; Herzog, Thomas J.; DiSaia, Philip J.; Copeland, Larry J.; Mannel, Robert S.; Birrer, Michael J.; Monk, Bradley J.

In: Journal of Clinical Oncology, Vol. 37, No. 26, 10.09.2019, p. 2317-2328.

Research output: Contribution to journalArticle

Tewari, KS, Burger, RA, Enserro, D, Norquist, BM, Swisher, EM, Brady, MF, Bookman, MA, Fleming, GF, Huang, H, Homesley, HD, Fowler, JM, Greer, BE, Boente, M, Liang, SX, Ye, C, Bais, C, Randall, LM, Chan, JK, Stuart Ferriss, J, Coleman, RL, Aghajanian, C, Herzog, TJ, DiSaia, PJ, Copeland, LJ, Mannel, RS, Birrer, MJ & Monk, BJ 2019, 'Final overall survival of a randomized trial of bevacizumab for primary treatment of ovarian cancer', Journal of Clinical Oncology, vol. 37, no. 26, pp. 2317-2328. https://doi.org/10.1200/JCO.19.01009
Tewari, Krishnansu S. ; Burger, Robert A. ; Enserro, Danielle ; Norquist, Barbara M. ; Swisher, Elizabeth M. ; Brady, Mark F. ; Bookman, Michael A. ; Fleming, Gini F. ; Huang, Helen ; Homesley, Howard D. ; Fowler, Jeffrey M. ; Greer, Benjamin E. ; Boente, Matthew ; Liang, Sharon X. ; Ye, Chenglin ; Bais, Carlos ; Randall, Leslie M. ; Chan, John K. ; Stuart Ferriss, J. ; Coleman, Robert L. ; Aghajanian, Carol ; Herzog, Thomas J. ; DiSaia, Philip J. ; Copeland, Larry J. ; Mannel, Robert S. ; Birrer, Michael J. ; Monk, Bradley J. / Final overall survival of a randomized trial of bevacizumab for primary treatment of ovarian cancer. In: Journal of Clinical Oncology. 2019 ; Vol. 37, No. 26. pp. 2317-2328.
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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.",
author = "Tewari, {Krishnansu S.} and Burger, {Robert A.} and Danielle Enserro and Norquist, {Barbara M.} and Swisher, {Elizabeth M.} and Brady, {Mark F.} and Bookman, {Michael A.} and Fleming, {Gini F.} and Helen Huang and Homesley, {Howard D.} and Fowler, {Jeffrey M.} and Greer, {Benjamin E.} and Matthew Boente and Liang, {Sharon X.} and Chenglin Ye and Carlos Bais and Randall, {Leslie M.} and Chan, {John K.} and {Stuart Ferriss}, J. and Coleman, {Robert L.} and Carol Aghajanian and Herzog, {Thomas J.} and DiSaia, {Philip J.} and Copeland, {Larry J.} and Mannel, {Robert S.} and Birrer, {Michael J.} and Monk, {Bradley J.}",
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TY - JOUR

T1 - Final overall survival of a randomized trial of bevacizumab for primary treatment of ovarian cancer

AU - Tewari, Krishnansu S.

AU - Burger, Robert A.

AU - Enserro, Danielle

AU - Norquist, Barbara M.

AU - Swisher, Elizabeth M.

AU - Brady, Mark F.

AU - Bookman, Michael A.

AU - Fleming, Gini F.

AU - Huang, Helen

AU - Homesley, Howard D.

AU - Fowler, Jeffrey M.

AU - Greer, Benjamin E.

AU - Boente, Matthew

AU - Liang, Sharon X.

AU - Ye, Chenglin

AU - Bais, Carlos

AU - Randall, Leslie M.

AU - Chan, John K.

AU - Stuart Ferriss, J.

AU - Coleman, Robert L.

AU - Aghajanian, Carol

AU - Herzog, Thomas J.

AU - DiSaia, Philip J.

AU - Copeland, Larry J.

AU - Mannel, Robert S.

AU - Birrer, Michael J.

AU - Monk, Bradley J.

PY - 2019/9/10

Y1 - 2019/9/10

N2 - 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.

AB - 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.

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