A large-scale real-world study has confirmed that the addition of bevacizumab to first-line chemotherapy for epithelial ovarian cancer (EOC) primarily benefits patients with high-risk prognostic factors, providing crucial validation of earlier clinical trial findings.
The BEV1L study, published in Cancer, examined data from 1,753 patients with stage III or IV epithelial ovarian cancer to evaluate the real-world outcomes associated with bevacizumab use in first-line treatment regimens. The findings align with post-hoc analyses from the GOG-0218 and ICON7 clinical trials conducted over a decade ago.
Real-World Evidence Supports Targeted Use of Bevacizumab
Researchers utilized the Flatiron Health database, comprising information from approximately 280 cancer clinics across the United States. The study included female patients diagnosed with ovarian cancer on or after January 1, 2016, who were 18 years or older with confirmed epithelial histology and stage III or IV disease at diagnosis.
Among the study population, 70.8% (1,240 patients) received first-line chemotherapy alone, while 29.2% (512 patients) received chemotherapy plus bevacizumab. Patients were further stratified based on the presence of high-risk prognostic factors, defined as having stage IV disease, stage III disease with visible residual disease, or stage III disease with no documentation of surgery.
The results demonstrated a clear distinction in treatment outcomes based on risk status:
- In patients with high-risk prognostic factors, the median real-world time to next treatment was significantly longer in the bevacizumab group compared to chemotherapy alone (13.6 months vs. 11.7 months; HR, 0.85; 95% CI, 0.73-0.99; P = 0.03)
- Patients without high-risk factors showed no significant difference in time to next treatment between treatment groups
- Overall survival was numerically longer for high-risk patients receiving bevacizumab (31.1 months vs. 27.4 months), though this difference narrowly missed statistical significance (HR, 0.84; 95% CI, 0.70-1.00; P = 0.052)
- No overall survival benefit was observed in patients without high-risk factors (61.4 months with bevacizumab vs. 63.2 months without; HR, 1.03; 95% CI, 0.68-1.55; P = 0.90)
Clinical Implications for Treatment Decision-Making
"These real-world results remain consistent with findings from the ICON7 and GOG-0218 trials and suggest that the clinical benefit from the addition of bevacizumab to first-line chemotherapy may be largely limited to patients with high-prognostic factors," the study authors concluded.
The findings are particularly relevant given the evolution of the treatment landscape since the original clinical trials were conducted. With additional maintenance treatment options now available, contemporary data helps clinicians identify which patients are most likely to benefit from bevacizumab.
Dr. Shannon Westin, a gynecologic oncologist not involved in the study, commented: "This real-world evidence reinforces what we've observed in clinical practice—that patient selection is critical when considering bevacizumab. These findings help us make more informed decisions about which patients should receive this treatment as part of their first-line regimen."
Study Limitations and Future Directions
The researchers acknowledged several limitations to their analysis. The database primarily comprised community oncology centers and only included patients treated in the United States, potentially limiting generalizability to academic centers or international settings.
Additionally, the study authors highlighted "a need to better understand why the addition of bevacizumab provides a greater clinical benefit in specific patient subgroups." This suggests future research should focus on identifying biological markers or mechanisms that might explain the differential response to bevacizumab based on risk status.
Historical Context of Bevacizumab in Ovarian Cancer
The original GOG-0218 trial demonstrated that adding bevacizumab to first-line chemotherapy followed by bevacizumab maintenance therapy significantly prolonged progression-free survival in patients with newly diagnosed, incompletely resected stage III or IV epithelial ovarian cancer compared with chemotherapy alone (HR, 0.72; 95% CI, 0.63-0.82).
Similarly, the ICON7 trial found improved progression-free survival with bevacizumab in patients with high-risk early-stage or advanced epithelial ovarian cancer compared to placebo (HR, 0.81; 95% CI, 0.70-0.94). However, neither trial demonstrated overall survival improvements in their overall study populations.
The BEV1L study provides important validation of these findings in a real-world setting, offering clinicians greater confidence in tailoring treatment approaches based on patient risk factors. As the treatment landscape for ovarian cancer continues to evolve, such evidence-based stratification of patients becomes increasingly valuable for optimizing outcomes while minimizing unnecessary treatment.
