At the 2010 American Society of Clinical Oncology Annual conference in Chicago, the Gynecologic Oncology Group(GOG) presented the results of the latest clinical trial for Avastin and ovarian cancer. GOG 218 (activated in October 2005) aims to randomly assign 2,000 patients in a three-arm placebo-controlled trial in which patients with stage III and IV disease receive paclitaxel and carboplatin, with or without bevacizumab (15 mg/kg every 21 days) for six courses, with a third arm continuing bevacizumab for an additional 48 weeks. Genentech, Inc., announced in February 2010 that the GOG Phase III study showed the combination of Avastin® (bevacizumab) and chemotherapy followed by maintenance use of Avastin alone increased the time women with previously untreated advanced ovarian cancer lived without the disease worsening (progression-free survival or PFS), compared to chemotherapy alone. Patients were randomly assigned to 3 treatment groups: paclitaxel 175 mg/m2 plus carboplatin area under curve (AUC) 6 cycles plus placebo maintenance; paclitaxel plus carboplatin and concurrent bevacizumab (15 mg/kg) and placebo maintenance; and paclitaxel plus carboplatin plus concurrent bevacizumab plus maintenance bevacizumab.Patients who received chemotherapy alone had a median progression-free survival of 10.3 months, compared with 11.2 months for those who received concurrent bevacizumab but placebo maintenance. GOG 218 study (Berger, ASCO 2009) only showed that, if the provider chooses to continue Avastin as maintenance, the result would be superior for the arm that included Avastin. It showed that Avastin maintenance is superior but did not answer the question of Avastin for the primary treatment itself. Women who received Avastin in combination with chemotherapy but did not continue maintenance use of Avastin did not have a longer progression free survival compared to those on chemotherapy alone. In other words, it showed that the two treatments are equivalent.
A recent 2010 abstract of ICON study presented at ESMO was supportive. Women with high-risk early or advanced ovarian cancer gained almost two months in progression-free survival (PFS) when the angiogenesis inhibitor bevacizumab (Avastin) was added to chemotherapy, results of a large international clinical trial showed. Patients who received bevacizumab in addition to carboplatin-paclitaxel chemotherapy had a median PFS of 19 months, compared with 17.3 months for those treated with chemotherapy alone. Preliminary survival data from the 1,500-patient ICON7 study show a trend toward fewer deaths in the bevacizumab group, but survival data will not be mature for another two years. This ICON7 trial was a randomized trial. The control arm of the trial was standard chemotherapy with carboplatin and paclitaxel given in the usual way for 6 cycles, 1 cycle of treatment every 3 weeks, and then no further treatment. In the research arm of the trial, patients were treated with chemotherapy and bevacizumab for 6 cycles and then received bevacizumab for a further 12 cycles of treatment, which made 18 cycles or 12 months of treatment in total. The primary endpoint for our trial was progression-free survival and the study showed that progression was delayed and occurred less frequently in patients treated with bevacizumab than in patients in the control arm.
NCCN on p. MS-8 says that unitl the data is more mature, it does not recommend routine use of Avastin to first line chemotherapy or routine maintenance. Society of Gynecologic Oncology is more supportive but not definitive. It says: ” SGO encourages patients and providers to discuss risks, benefits and costs associated with use of bevacizumab as a component of upfront treatment and maintenance therapy.”
At this point, the presented data had been peer-reviewed and published. The use of bevacizumab during and up to 10 months after carboplatin and paclitaxel chemotherapy prolongs the median progression-free survival by about 4 months in patients with advanced epithelial ovarian cancer. It has not been incorproated into NCCN guidelines as of January of 2012 but seems destined to be.
IRobert A. Burger, M.D., Mark F. Brady, Ph.D., Michael A. Bookman, M.D., Gini F. Fleming, M.D., Bradley J. Monk, M.D., Helen Huang, M.S., Robert S. Mannel, M.D., Howard D. Homesley, M.D., Jeffrey Fowler, M.D., Benjamin E. Greer, M.D., Matthew Boente, M.D., Michael J. Birrer, M.D., Ph.D., and Sharon X. Liang, M.D. for the Gynecologic Oncology Group ,Incorporation of Bevacizumab in the Primary Treatment of Ovarian Cancer N Engl J Med 2011; 365:2473-2483December 29, 2011
Perren T, Swart AM, Pfisterer J, et al: ICON7: A phase III randomized gynaecologic cancer intergroup trial of concurrent bevacizumab and chemotherapy followed by maintenance bevacizumab versus chemotherapy alone in women with newly diagnosed epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer. Program and abstracts of the 35th European Society for Medical Oncology (ESMO) Congress; October 8-12, 2010; Milan, Italy. Abstract LBA4.
Burger RA, Brady MF, Bookman MA, et al. Phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC), or fallopian tube cancer (FTC): A Gynecologic Oncology Group study. J Clin Oncol. 2010;28:abstract LBA1, ASCO Annual Meeting Proceedings (Post-Meeting Edition). Available at: http://meeting.ascopubs.org/cgi/content/abstract/28/18_suppl/LBA1
Robert A. Burger, Experience With Bevacizumab in the Management of Epithelial Ovarian Cancer, Journal of Clinical Oncology, Vol 25, No 20 (July 10), 2007: pp. 2902-2908
Burger R, Brady MF, Bookman MA, et al: Phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC), or fallopian tube cancer (FTC): A Gynecologic Oncology Group study. 2010 ASCO Annual Meeting. Abstract LBA1. Presented June 6, 2010.
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