Increasing the duration of bevacizumab treatment in the frontline setting did not improve progression-free survival for patients with advanced ovarian cancer.
Increasing the treatment time of bevacizumab (Avastin) beyond 15 months did not improve progression-free survival (PFS) in newly diagnosed patients with stage IIB-IV ovarian cancer, according to data from the phase 3 BOOST trial (NCT01462890) published in the Journal of Clinical Oncology.
Among 2 cohorts of patients with ovarian cancer receiving bevacizumab, there was no difference in PFS between the treatment arms (HR, 0.99; 95% CI, 0.85-1.15; P = .90). The median PFS with 15 months of treatment was 24.2 (95% CI, 22.2-26.5), and extended treatment of 30 months yielded a median PFS of 26.0 months. (95% CI, 23.7-29.7). For restricted mean PFS, the outcomes were 39.5 vs 39.3 months, respectively. Overall survival (OS) outcomes were also similar between the 2 arms (HR, 1.04; 95% CI, 0.87-1.23; P = .68). Moreover, the rates of adverse effects (AEs) of interest between 15 months and 30 months of treatment were 29% and 34%. Reported AEs were consistent with previous reports with bevacizumab.
“Extending the duration of maintenance bevacizumab therapy did not significantly improve PFS and therefore, the approved duration of bevacizumab [15 mg/kg once every 3 weeks for 15 months] remains a standard-of-care regimen… in the front-line setting,” study authors wrote.
Two prior trials have demonstrated that early and continuous treatment with bevacizumab, a monoclonal antibody, in addition to carboplatin and paclitaxel chemotherapy, confers a PFS benefit to patients with ovarian cancer. However, prior this this trial, the optimal treatment duration remained unknown.
The BOOST trial was designed to determine the best duration of frontline bevacizumab in this setting and investigators extended treatment length from 15 months (as used in 1 of the 2 trials) to 30 months to assess if longer exposure would improve efficacy.
Enrolled patients had histologically confirmed, newly diagnosed, stage IIB-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer (any grade or histologic subtype). Patients also needed to have received primary cytoreductive surgery at least 8 weeks before starting chemotherapy and more than 4 weeks before the planned start date of bevacizumab treatment. The trial enrolled a total 927 patient between November 11, 2011, and August 6, 2013.
Investigator-assessed PFS represented the trials’ primary end point. Secondary end points included OS, objective response rate, health-related quality of life, safety, and tolerability. The median OS with 15-month and 30-month treatment was 54.3 and 60.0 months, respectively. The restricted mean OS was 60.4 vs 60.8 months, respectively.
No difference in objective response rates were observed; objective responses occurred in 26% and 27% of patients (P = .87).
AEs of any-grade occurred in great numbers in both treatment arms (99% vs 99%). The rates of grade 3 or worse AEs were also similar between both arms (63% vs 68%), as were the rates of serious AEs (44% vs 46%). A serious AE was defined as any event that resulted in death, inpatient hospitalization, the prolongation of existing hospitalization, was life threatening, or induced a disability.
Extended treatment with bevacizumab was linked to a slight increase in grade 3 or greater hypertension or proteinuria; however, that was the only special AEs of interest to be induced by longer treatment.
Study authors acknowledged that the trial did not assess BRCA mutation status and therefore, any potential imbalanced between treatment arms cannot be excluded. Moreover, they noted that the open-label design with no blinded independent review of PFS may represent a limitation; however, investigators noted that patients may not be willing to receive placebo for up to 15 months.
“Longer treatment duration with bevacizumab for up to 30 months did not improve PFS or OS in patients with primary epithelial ovarian, fallopian tube, or peritoneal cancer,” study authors concluded. “A bevacizumab treatment duration of 15 months remains the standard of care.”
Pfisterer J, Joly F, Kristensen G, et al. Optimal treatment duration of bevacizumab as front-line therapy for advanced ovarian cancer: AGO-OVAR 17 BOOST/GINECO OV118/ENGOT Ov-15 open-label randomized phase III trial. J Clin Oncol. Published online November 4, 2022. doi:10.1200/JCO.22.01010