Efficacy and long-term safety with bevacizumab included in neoadjuvant and adjuvant therapies in patients with advanced ovarian cancer: Results of the ANTHALYA trial.

Abstract

5538 Background: ANTHALYA showed that neoadjuvant Bevacizumab (B) added to Carboplatin and Paclitaxel (CP) was well tolerated and achieved encouraging complete resection rates at IDS (58.6%) in unresectable FIGO stage IIIC/IV ovarian, tubal or peritoneal adenocarcinoma (EJC 2017;70:133–42). We report response rates, PFS and long-term safety. Methods: Patients (pts) in ANTHALYA were randomized 2:1 to 4 cycles (c) of neoadjuvant CP ±3 c of B (15 mg/kg), IDS for eligible patients, then 1 c of CP + 3 c CPB + 21 c of B. Response and progression were evaluated by RECIST 1.1 using CT scan and CA-125. Circulating tumor cell counts (CTC) were evaluated at baseline, c2 and IDS. Results: 95 pts were treated in CP (n=37) or BCP (n=58) groups (mean study duration were 16.1 months [mo] and 16.9 mo, respectively). 80 pts (CP: 81% / BCP: 88%) had a CA-125 response (50% reduction in CA-125 level) before IDS. Objective response rates were 65% (62% CP / 67% BCP) before IDS (28 days after c4), 46% at c8 (46% CP/ 47% BCP) and 19% at c26 (19% CP/ 19% BCP). 24 (64.9%) CP pts and 26 (44.8%) BCP pts progressed during follow up (median PFS 21.2 mo [95%CI: 14.5, 26.7] and 23.5 mo [18.5, 30.6], respectively). Median PFS was respectively: 25.8 mo (21.0, 30.0) and 17.1 mo (13.5, 22.2) for pts with/without complete resection at IDS; 21.0 mo (15.0, 25.4) and 25.8 mo (18.5, 27.2) for pts with/without baseline CTCs (n=29 / 59); 21.8 mo (17.5, 27.1) and 22.2 mo (15.3, 38.0) for pts with FIGO IIIC and IV tumors. 36 pts did not receive adjuvant therapy within the study (21 were unresectable for IDS), 59 pts (57% CP / 66% BCP) received it. Of those, 34 pts (52% CP / 61% BCP) had Grade ≥3 adverse events including neutropenia (29% CP / 34% BCP), HBP (10% CP / 8% BCP), proteinuria (10% CP / 0% BCP), deep venous thrombosis (5% CP / 3% BCP), pulmonary embolism (0% CP / 8% BCP). Conclusions: Neoadjuvant BCP followed by IDS and adjuvant BCP achieves high response rates and extended PFS with an acceptable toxicity in this specific population of pts with FIGO stage IIIC/IV ovarian, tubal or peritoneal adenocarcinoma not eligible for primary debulking surgery. IDS outcome and CTC counts should be further explored as long term prognostic factors. Clinical trial information: NCT01739218.