Optimization of intra-peritoneal chemotherapy: Randomized phase II GERCOR CHIMOVIP study.

5519 Background: Upon initiation, our study built on three phase III studies indicating a significant increase in long-term overall survival (OS) with intraperitoneal (IP) chemotherapy. These trials incorporated patients with macroscopic residual disease (RD) <1cm. We hypothesized higher efficacy when administering IP chemotherapy early to patients achieving total completeness of cytoreduction (CC0) either at first surgery or at interval surgery (<3 months), and that pathological complete response (pCR) a surrogate of cure and OS. Cisplatin, the platinum salt recommended for IP administration of chemotherapy, was administered with epirubicin, chosen over paclitaxel to prevent neuropathy. To avoid potential biases, a control group, treated with conventional IV carboplatin and paclitaxel and undergoing the same surgical procedures, was included. Methods: Eligible patients were aged <75 years and had epithelial ovarian cancer stage III or IV (pleura and lymph node only).In both arms patients had initial surgery and interval surgery after 3 chemotherapy cycles in the presence of residual disease. A second-look procedure was performed after 6 cycles in all CC0 patients. The IP arm, patients with CC0 at the first surgery received 6 cycles of IP cisplatin 80 mg/m² and intravenous (IV) epirubicin 60 mg/m². Those with RD at first surgery received 3 IV cycles of cisplatin-epirubicin, followed by 3 IP cycles of cisplatin and IV epirubicin in if CC0 was achieved at interval laparotomy. In the control arm patients received 6 cycles of IV carboplatin AUC6 with paclitaxel 80 mg/m² IV on days 1, 8, and 15. The primary endpoint was pathological complete response (pCR) rate. A Simon’s two stage design with an interim analysis planned after the inclusion of 18 evaluable patients in the experimental arm was used to test the following hypotheses: H 0 : a pCR rate of ≤ 20% (uninteresting) and H 1 : a pCR rate of ≥ 40% (expected). Results: A total of 43 patients were randomized; 21 in the experimental IP arm and 22 in the control arm. At the interim analysis, 12 patients (66.7%) in the experimental arm and 11 (61.1%) in the control arm had pCR. A significant imbalance favoring the standard arm was observed for age, preoperative HE4, and low-grade tumor. There was no safety issue, with grade 3-4 toxicities lower in the IP arm (31.6% vs. 55.5% in the standard arm). With a median follow-up of 4.6 years 95%CI (4.2-5.0), median event free survival (EFS) and OS were respectively 3.0 years and not reached in the IP arm and 1.4 years and 3.5 years respectively in the IV arm (Table below). Conclusions: While both arms showed ahigh pCR rate, EFS suggests that pCR is not a good surrogate for OS. The observed benefits in EFS and OS in the IP arm suggest a greater advantage of IP for CC0 patients. Clinical trial information: NCT03025477 . [Table: see text]