The aim of the AGO-OVAR 17 Bevacizumab Ovarian Optimal Standard Treatment (BOOST) study was to evaluate the optimal treatment duration of front-line bevacizumab-containing therapy for patients with newly diagnosed stage IIB-IV epithelial ovarian, Fallopian tube, or peritoneal cancer, specifically to determine whether extending bevacizumab treatment duration from 15 months to 30 months improves efficacy. Prof. Jacobus Pfisterer of the AGO Study Group and Gynaecologic Oncology Centre in Kiel, Germany and colleagues reported on 4 November 2022 in the Journal of Clinical Oncology that longer treatment duration with bevacizumab for up to 30 months did not improve progression-free survival (PFS) or overall survival (OS) in this setting. A bevacizumab treatment duration of 15 months remains the standard of care.
Two studies, GOG-0218 and AGO-OVAR 11/ICON7, demonstrated that early and continuous addition of bevacizumab to standard carboplatin and paclitaxel chemotherapy statistically significantly improved PFS. In GOG-0218, bevacizumab was administered at a dose of 15 mg/kg once every 3 weeks for 15 months, whereas in AGO-OVAR 11/ICON7, patients received bevacizumab 7.5 mg/kg once every 3 weeks for 12 months. In both studies, the PFS benefit reached its maximum at the time point of highest cumulative bevacizumab exposure immediately after the last bevacizumab cycle. However, the optimal bevacizumab treatment duration remained unknown.
In the AGO-OVAR 17 BOOST/GINECO OV118/ENGOT Ov-15, multicentre, open-label, randomised phase III study, patients with newly diagnosed International Federation of Gynecology and Obstetrics stage IIB-IV epithelial ovarian, Fallopian tube, or peritoneal cancer underwent primary cytoreductive surgery followed by 6 cycles of chemotherapy containing paclitaxel 175 mg/m2 plus carboplatin area under the curve 5 once every 3 weeks and bevacizumab 15 mg/kg once every 3 weeks. Patients were randomly assigned 1:1 to receive bevacizumab for either 15 or 30 months, stratified by stage/residual tumour. The primary endpoint was investigator-assessed PFS according to RECIST v1.1. Secondary endpoints included OS, safety, and tolerability.
Between November 2011 and August 2013, a total of 927 women were randomly assigned. There was no difference in PFS between treatment arms (hazard ratio [HR] 0.99; 95% confidence interval [CI] 0.85 to 1.15; unstratified log-rank p = 0.90). Median PFS was 24.2 versus 26.0 months with standard versus extended duration of bevacizumab. Restricted mean PFS was 39.5 versus 39.3 months, respectively.
There was no OS difference between treatment arms (HR 1.04; 95% CI 0.87 to 1.23; p = 0.68). Serious/non-serious adverse events of special interest occurred in 29% versus 34% of patients in the standard versus extended bevacizumab duration arms and were consistent with the known safety profile.
The authors concluded that the primary objective of the AGO-OVAR 17 BOOST/GINECO OV118/ENGOT Ov-15 study was not met as extending the duration of maintenance bevacizumab did not significantly improve PFS. Therefore, the approved duration of bevacizumab 15 mg/kg once every 3 weeks for 15 months remains a standard of care regimen. The authors commented that median PFS exceeding 2 years is the longest reported to date with the standard front-line bevacizumab regimen.
The only other large prospective study of front-line bevacizumab-containing treatment showing PFS exceeding 2 years is the single-arm phase IIIB ROSiA study, in which bevacizumab was administered for up to 24 months. The most plausible hypothesis for the median PFS of 25.5 months in ROSiA was the extended treatment duration of bevacizumab, but evidence from the AGO-OVAR 17 BOOST contradicts this hypothesis.
The authors commented that a limitation of the AGO-OVAR 17 BOOST study is the lack of information on BRCA mutation status. In current practice, BRCA mutation status is an important predictive and prognostic factor and plays a critical role in treatment decision making, but when the study was designed, BRCA mutation status was rarely collected even in the context of clinical trials.
Financial support and drug supply was provided by F. Hoffmann-La Roche Ltd.
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. JCO; Published online 4 November 2022. DOI: 10.1200/JCO.22.01010