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Abstract
Background Bevacizumab is an approved treatment after primary debulking surgery for ovarian cancer. However, there is limited information on bevacizumab added to neoadjuvant chemotherapy before interval debulking surgery.
Objective To evaluate neoadjuvant bevacizumab in a randomized phase II trial.
Methods Patients with newly diagnosed stage III/IV high-grade serous/endometrioid ovarian cancer were randomized to receive four cycles of neoadjuvant chemotherapy with or without ≥3 cycles of bevacizumab 15 mg/kg every 3 weeks. After interval debulking surgery, all patients received post-operative chemotherapy (three cycles) and bevacizumab for 15 months. The primary end point was complete macroscopic response rate at interval debulking surgery.
Results Of 68 patients randomized, 64 completed four neoadjuvant cycles; 22 of 33 (67%) in the chemotherapy-alone arm and 31 of 35 (89%) in the bevacizumab arm (p=0.029) underwent surgery. The complete macroscopic response rate did not differ between treatment arms in either the intention-to-treat population of 68 patients (6.1% vs 5.7%, respectively; p=0.25) or the 55 patients who underwent surgery (8.3% vs 6.5%; p=1.00). There was no difference in complete cytoreduction rate or progression-free survival between the treatment arms. During neoadjuvant therapy, grade ≥3 adverse events were more common with chemotherapy alone than with bevacizumab (61% vs 29%, respectively; p=0.008). Intestinal (sub)occlusion, fatigue/asthenia, abdominal infection, and thrombocytopenia were less frequent with bevacizumab. The incidence of grade ≥3 adverse events was 9% in the control arm versus 16% in the experimental arm in the month after surgery.
Conclusions Adding three to four pre-operative cycles of bevacizumab to neoadjuvant chemotherapy for unresectable disease did not improve the complete macroscopic response rate or surgical outcome, but improved surgical operability without increasing toxicity. These results support the early integration of bevacizumab in carefully selected high-risk patients requiring neoadjuvant chemotherapy for initially unresectable ovarian cancer.
- bevacizumab
- complete macroscopic response rate
- interval debulking surgery
- ovarian cancer
- neoadjuvant chemotherapy
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Footnotes
Contributors Study concept and design, quality control of data and algorithms, data analysis and interpretation, statistical analysis, manuscript preparation: YGG, AdJF; Data acquisition, manuscript editing and manuscript review: all authors.
Funding This study was funded by Roche Farma, S.A.
Competing interests YGG has received travel expenses and registration costs for attending scientific meetings from Roche Farma Spain, AstraZeneca, and PharmaMar; and speaker honoraria from Roche Farma, Spain. CM has received travel expenses and registration costs for attending scientific meetings from Roche Farma Spain, AstraZeneca, and PharmaMar; and speaker honoraria from Roche Farma Spain. PB-G has received speaker honoraria and travel expenses/registration fees to attend scientific meetings from Roche Farma Spain, AstraZeneca, and PharmaMar; and honoraria for advisory roles for Roche Farma Spain and AstraZeneca. AGM has received honoraria for speaker engagements and advisory roles from Roche, Tesaro, AstraZeneca, and PharmaMar. All remaining authors have declared no conflicts of interest.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.