Previously reported safety data from ANTHALYA indicated that adding 3 cycles of bevacizumab (B) to neoadjuvant carboplatin and paclitaxel (CP) was feasible in FIGO stage IIIc/IV ovarian, tubal or peritoneal adenocarcinoma, initially deemed unresectable. BCP had a good safety profile and a pre-specified stopping rule for toxicity based on Bev-related adverse events (AEs) of special interest was not reached. Here, we evaluated if BCP could help to achieve optimal debulking, as measured by the complete resection rate (CRR) at interval debulking surgery (IDS).
In this multicenter, open-label, randomized non comparative Phase II study, patients were randomized 2:1 to 4 cycles of neoadjuvant CP ±3 cycles of B (15 mg/kg). IDS was scheduled 28 ±7 days after the last neoadjuvant treatment course. The primary objective was to assess the superiority of the CRR at IDS (defined as a Completeness of Cytoreduction score [CC] of 0) in the BCP group compared to a reference rate of 45% (Vergote et al. N Engl J Med 2010;363:943-53) using the Fleming A'Hern method (p0 = 45%; p1 = 65%; α = 5%; � = 10%).
205 patients were screened at 15 French sites and 95 were randomized and included in the modified intention to treat population. Median age was 63 years, 92% had ECOG-PS 0/1, with 70% FIGO stage IIIc and 30% stage IV tumors. In the BCP group (58 patients) the CRR at IDS was 58.6% (34 patients) with a lower confidence limit of 47.0%, significantly higher than the prespecified minimum threshold of 45%. IDS was performed in 69% (40 patients) of whom 85% had a complete resection. The CRR was 63.5% in patients with ≥2 cycles of Bev (52 patients). In the CP group (37 patients), IDS was done in 22 (60%) patients with a CRR of 51.4%.
The study primary objective was met as the CRR was significantly higher than the previously reported reference rate. Adding Bev to neoadjuvant CP achieved an encouraging CRR at IDS in patients with initially unresectable FIGO stage IIIc/IV ovarian, tubal or peritoneal adenocarcinoma.
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Legal entity responsible for the study
R. Rouzier: Advisory board. S. Gouy, F. Selle, C. Pomel, E. Chereau, P. Cottu, F. Joly: Board Y. Ghazi, J. Dupin: Employee. All other authors have declared no conflicts of interest.