OV21/PETROC: A randomized Gynecologic Cancer Intergroup (GCIG) phase II study of intraperitoneal (IP) versus intravenous (IV) chemotherapy following neoadjuvant chemotherapy and optimal debulking surgery in epithelial ovarian cancer (EOC).

Abstract

LBA5503 Background: The aim of this 2 stage randomized trial was to evaluate whether women undergoing neoadjuvant IV chemotherapy followed by delayed debulking surgery benefit from the addition of IP/IV treatment after surgery. Methods: Stage 1 was a randomized 3-arm design including 2 IP platinum regimens: 153 women who received 3-4 courses of IV platinum-based chemo for stage IIB-III (IV pleural effusion only) EOC followed by optimal debulking surgery ( < 1 cm) were randomized to: ARM1 D1 IV paclitaxel (pacli) 135mg/m2 + IV Carboplatin AUC 5/6 with d8 pacli IV 60 mg/m2 Q 21d X3; ARM 2 D1 IV pacli 135mg/m2 + IP cisplatin (Cis) 75 mg/m2 and d8 IP pacli 60 mg/m2 Q21d X3; or ARM 3 d1 IV pacli 135mg/m2+ IP Carboplatin AUC 5/6 and d8 IP pacli 60mg/m2 Q21dX3. A planned DSMC review confirmed dropping ARM2 (IP cis) and continuing study as an expanded phase II comparing 200 patients randomized to ARMs 1 and 3, which has 80% power to detect a 19% difference in progression rate at 9 mo (PD9, primary endpoint), 2-sided α = 0.05. Progression free survival (PFS) and overall survival (OS) are secondary efficacy endpoints. Results: Between 2009 and May 2015, 275 patients were accrued: n = 101 Arm 1, 72 Arm 2, 102 Arm 3. Median age was 62; 81.8%s had stage 3 C disease; 12.7% stage IV. Baseline characteristics were balanced between arms. Median number of cycles was 3 all arms; completion rates Arm 1, 93.7% and Arm 3, 84.8%. Intention to treat PD9 rates: Arm 1: 38.6% (95% CI 29.1%- 48.8%) and Arm 3: 24.5% (95% CI 16.5%-34.0%); p = 0.065 stratified; p = 0.03 unstratified. Per protocol (eligible, received > one dose of protocol therapy) PD9 rates: Arm 1: 42.2% (95% CI 31.9%- 53.1%), Arm 3: 23.3% (95% CI 15.1%-33.4%); p = 0.03 stratified; p = 0.01 unstratified. Median PFS 11.3 mo (Arm1) and 12.5 mo (Arm 3); HR 0.82 (95% CI 0.57 - 1.17); p = 0.27. Median OS: 38.1 mo (Arm 1) and 59.3 mo (Arm 3); HR 0.80 (95% CI 0.47-1.35) p = 0.40. Adverse events > Gr 3 rates: 23% (Arm 1) and 16% (Arm 3) (p = 0.24). Conclusions: The IP carboplatin based regimen, post neoadjuvant chemotherapy and debulking surgery, is well tolerated and associated with a lower PD9 rate compared to IV therapy. Clinical trial information: NCT00993655.