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.
RCT Entities:
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: Bradley J Monk; Andrés Poveda; Ignace Vergote; Francesco Raspagliesi; Keiichi Fujiwara; Duk-Soo Bae; Ana Oaknin; Isabelle Ray-Coquard; Diane M Provencher; Beth Y Karlan; Catherine Lhommé; Gary Richardson; Dolores Gallardo Rincón; Robert L Coleman; Thomas J Herzog; Christian Marth; Arija Brize; Michel Fabbro; Andrés Redondo; Aristotelis Bamias; Marjan Tassoudji; Lynn Navale; Douglas J Warner; Amit M Oza Journal: Lancet Oncol Date: 2014-06-17 Impact factor: 41.316
Authors: Christopher P Childers; Kimberly K Childers; Melinda Maggard-Gibbons; James Macinko Journal: J Clin Oncol Date: 2017-08-18 Impact factor: 44.544
Authors: Elizabeth L Christie; Sian Fereday; Ken Doig; Swetansu Pattnaik; Sarah-Jane Dawson; David D L Bowtell Journal: J Clin Oncol Date: 2017-02-13 Impact factor: 44.544
Authors: Andreas du Bois; Gunnar Kristensen; Isabelle Ray-Coquard; Alexander Reuss; Sandro Pignata; Nicoletta Colombo; Ursula Denison; Ignace Vergote; Jose M Del Campo; Petronella Ottevanger; Martin Heubner; Thomas Minarik; Emmanuel Sevin; Nikolaus de Gregorio; Mariusz Bidziński; Jacobus Pfisterer; Susanne Malander; Felix Hilpert; Mansoor R Mirza; Giovanni Scambia; Werner Meier; Maria O Nicoletto; Line Bjørge; Alain Lortholary; Martin Oliver Sailer; Michael Merger; Philipp Harter Journal: Lancet Oncol Date: 2015-11-16 Impact factor: 41.316
Authors: James S Ferriss; James J Java; Michael A Bookman; Gini F Fleming; Bradley J Monk; Joan L Walker; Howard D Homesley; Jeffrey Fowler; Benjamin E Greer; Matthew P Boente; Robert A Burger Journal: Gynecol Oncol Date: 2015-07-26 Impact factor: 5.482
Authors: John K Chan; Mark F Brady; Richard T Penson; Helen Huang; Michael J Birrer; Joan L Walker; Paul A DiSilvestro; Stephen C Rubin; Lainie P Martin; Susan A Davidson; Warner K Huh; David M O'Malley; Matthew P Boente; Helen Michael; Bradley J Monk Journal: N Engl J Med Date: 2016-02-25 Impact factor: 91.245
Authors: Kathleen Moore; Nicoletta Colombo; Giovanni Scambia; Byoung-Gie Kim; Ana Oaknin; Michael Friedlander; Alla Lisyanskaya; Anne Floquet; Alexandra Leary; Gabe S Sonke; Charlie Gourley; Susana Banerjee; Amit Oza; Antonio González-Martín; Carol Aghajanian; William Bradley; Cara Mathews; Joyce Liu; Elizabeth S Lowe; Ralph Bloomfield; Paul DiSilvestro Journal: N Engl J Med Date: 2018-10-21 Impact factor: 91.245
Authors: Andreas du Bois; Anne Floquet; Jae-Weon Kim; Joern Rau; Josep M del Campo; Michael Friedlander; Sandro Pignata; Keiichi Fujiwara; Ignace Vergote; Nicoletta Colombo; Mansoor R Mirza; Bradley J Monk; Rainer Kimmig; Isabelle Ray-Coquard; Rongyu Zang; Ivan Diaz-Padilla; Klaus H Baumann; Marie-Ange Mouret-Reynier; Jae-Hoon Kim; Christian Kurzeder; Anne Lesoin; Paul Vasey; Christian Marth; Ulrich Canzler; Giovanni Scambia; Muneaki Shimada; Paula Calvert; Eric Pujade-Lauraine; Byoung-Gie Kim; Thomas J Herzog; Ionel Mitrica; Carmen Schade-Brittinger; Qiong Wang; Rocco Crescenzo; Philipp Harter Journal: J Clin Oncol Date: 2014-09-15 Impact factor: 44.544
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: Gynecol Oncol Date: 2020-07-26 Impact factor: 5.482
Authors: Benjamin M Kahn; Alfredo Lucas; Rohan G Alur; Maximillian D Wengyn; Gregory W Schwartz; Jinyang Li; Kathryn Sun; H Carlo Maurer; Kenneth P Olive; Robert B Faryabi; Ben Z Stanger Journal: J Clin Invest Date: 2021-01-19 Impact factor: 14.808
Authors: Karen A Cadoo; Rachel N Grisham; Roisin E O'Cearbhaill; Nicole N Boucicaut; Melissa Henson; Alexia Iasonos; Qin Zhou; Debra M Sarasohn; Jacqueline Gallagher; Sara Kravetz; Dmitriy Zamarin; Vicky Makker; Paul J Sabbatini; William P Tew; Carol Aghajanian; Jason A Konner Journal: Gynecol Oncol Date: 2020-01-17 Impact factor: 5.482