In the prospective, multicentric, international, phase III CHIPOR trial, #HIPEC significantly improved OS and peritoneal PFS of women with first platinum-sensitive relapse of epithelial ovarian cancer (EOC) treated with second-line platinum-based CT followed by secondary complete cytoreductive surgery.

In this randomized trial, 415 eligible patients with first platinum-sensitive relapse (platinum-free interval of ≥6 months) of EOC who received 6 cycles of platinum and taxane based CT ± bevacizumab, and those amenable to a complete cytoreductive surgery at the end of CT were randomly assigned to receive HIPEC (cisplatin 75 mg/m² at 41°C for 60 min) or not. Randomization was performed during complete cytoreductive surgery, stratified by center, surgical outcome (no residual disease vs residual <0.25 cm), platinum-free interval before relapse, and PARP inhibitor use (yes vs no). The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), peritoneal PFS, patient-reported outcomes, safety, and postoperative morbidity and mortality (≤60 days after surgery).

Baseline characteristics were balanced between treatment arms, 35% received bevacizumab in the control group and 31% in the HIPEC group, median Platinum free interval (PFI) was 17.8m in the control group and 17.4m in the HIPEC group. The majority of patients, 91%, completed all six cycles of chemotherapy. Additionally, 87% achieved no macroscopic residual (CC0) after surgery. In terms of BRCA mutation, 31% in control group and 29% in the HIPEC group were BRCA mutated. Furthermore, maintenance PARP inhibitors was received in 22% of control group and 17% of HIPEC group.

At the data cutoff (Jan 8, 2023), after a median follow-up of 6.2 years, HIPEC significantly improved the OS and reduced the hazard of death by 31%, median OS was 54.3m in the HIPEC group vs 45.8m in the control group (HR=0.69, P=0.02). PFS (secondary end point) was improved by the addition of HIPEC, median PFS was 10.2m vs 9.8m (HR=0.82, 95% CI (0.64–1.06)), Peritoneal PFS was significantly improved, median Peritoneal PFS was 13.1m and 12.2m in the HIPEC and control groups respectively (HR=0.71, 95% CI (0.54–0.94))

CHIPOR Is the largest prospective randomized trial that demonstrates a meaningful improvement in overall survival for HIPEC in relapsed platinum sensitive EOC. However, it is important to further comprehend the impact of patient-reported outcomes, the influence of BRCA status, and exposure to bevacizumab on the response to HIPEC and subsequent therapy.