Longer bevacizumab therapy did not improve survival in advanced ovarian cancer
Click Here to Manage Email Alerts
When added to chemotherapy, extending the duration of bevacizumab treatment from 15 to 30 months failed to improve progression-free survival or overall survival in patients with epithelial ovarian, fallopian tube or peritoneal cancer, according to a study presented at the ASCO Annual Meeting.
“The GOG-218 and ICON/AGO OVAR 11 trials revealed that the early and continuous addition of bevacizumab [Avastin, Genentech] to standard carboplatin and paclitaxel chemotherapy for 15 and 12 months, respectively, statistically significantly improves PFS,” Jacobus Pfisterer, MD, PhD, from the AGO Study Group and Gynecologic Oncology Center in Kiel, Germany, said during a presentation of the data. “In both trials, the PFS benefit reached its maximum at the time point of highest cumulative bevacizumab exposure immediately after the last bevacizumab cycle.”
The goal of the current randomized trial, Pfisterer noted, was to assess whether extending treatment to 30 months would further improve efficacy.
From November 2011 to August 2013, Pfisterer and colleagues randomly assigned 927 patients with FIGO stage IIb to IV epithelial ovarian, fallopian tube or peritoneal cancer to chemotherapy (paclitaxel 175 mg/m2 and carboplatin AUC5 every 3 weeks) plus the standard 15 months of bevacizumab or an experimental 30 months of bevacizumab.
To qualify for study inclusion, patients had to have adequate bone marrow, liver and renal function; adequate coagulation parameters; and a life expectancy longer than 3 months. Treatment had to be initiated within 8 weeks after primary cytoreductive surgery.
The median age of patients was 61 years, 84% had epithelial ovarian cancer, 85% had ECOG performance status of 0 or 1, 50% had no residual tumor and 79% had high-grade serous histology.
After a median follow-up of 85 months, the median PFS — the primary endpoint — was 24.2 months among patients who received 15 months of bevacizumab vs. 26 months among patients who received 30 months of bevacizumab (HR = 0.99; 95% CI, 0.85-1.15). Due to evidence of non-proportional distribution of events, the researchers also performed a restricted mean analysis, which showed a mean PFS of 39.5 months in both treatment arms, Pfisterer said.
Results revealed no significant differences in PFS with shorter vs. longer bevacizumab therapy in subgroup analyses of patients with FIGO IIB or IIIC cancers with or without residual tumors. Additionally, the median OS did not differ significantly between the shorter and longer treatment arms (54.3 vs. 60 months; HR = 1.04; 95% CI, 0.87-1.23), which was also supported by a restricted mean analysis.
Pfisterer noted that 99% of patients developed an adverse event, with more patients in the prolonged bevacizumab treatment arm experiencing an adverse event or adverse event of special interest compared with the shorter bevacizumab treatment arm (38% vs. 32%). Notably, more patients who received bevacizumab for 30 months vs. 15 months developed hypertension (grade 3 or higher; 25% vs. 20%) and proteinuria (grade 3 or higher; 4% vs. 2%). However, rates of intestinal perforation or fistula and thromboembolic events were similar between treatment arms.
For both carboplatin and paclitaxel, the relative dose intensity was approximately 95% in both treatment arms. For bevacizumab, the relative dose intensity was approximately 97% in total, 97% during the chemotherapy phase and 97% during the maintenance phase, which did not differ significantly between treatment arms.
“Although the median PFS of about 2 years was longer than in the original trials, longer treatment with bevacizumab for up to 30 months improved neither PFS nor OS in patients with primary epithelial ovarian, fallopian tube or peritoneal cancer,” Pfisterer said. “The duration of treatment for bevacizumab with 15 months as part of first-line treatment in advanced ovarian cancer remains standard of care.”
Further analyses, such as quality of life studies, are ongoing, according to Pfisterer.
Collapse
Pfisterer J, et al. Abstract 5501. Presented at: ASCO Annual Meeting; June 4-8, 2021 (virtual meeting).
Click Here to Manage Email Alerts