Hyperthermic Intraperitoneal Chemotherapy for Recurrent Ovarian Cancer (CHIPOR): A Randomized, Open-Label, Phase 3 Trial

The leading cause of death due to gynecological cancer is from ovarian cancer. Long-term survival is associated with com plete surgical resection and a prolonged platinum-free interval. Relapse of ovarian cancer typically occurs in the peritoneum. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a single procedure that takes place during surgery, which is designed to improve the treatment of any residual disease. Previous studies have shown HIPEC to be effective during primary treatments, but there is little reliable evidence surrounding this treatment for recurrent ovarian cancer. This study proposes a new approach to treatment of recurrence by offering platinum-based chemotherapy followed by complete cytoreductive surgery with or without HIPEC for the first relapse of ovarian cancer after anintervalofatleast6monthswithouttreatment. This was a multicenter, open-label, randomized, phase 3 trial taking place in 31 facilities in France, Belgium, Spain, and Canada. Inclusion criteria were patients with epithelial ovarian, primary peritoneal, or fallopian tube carcinoma with recurrence at least 6 months after completing the first-line chemotherapy treatment, no distant metastases other than metastatic pleural effusion and inguinal lymphadenopathy, age 18 years or older, and normal renal function. Exclusion criteria were hypersensitivity to cisplatin, prior antiangiogenic therapy within 2 months of surgery, nonepithelial ovarian histology, previous HIPEC, uncontrolled infection, and potential need for more than 2 gastrointestinal resections. The primary outcome for this study was overall survival (OS), mean ing the length of time between randomization and death from any cause. Secondary outcomes included progression-free survival, pain, health-related quality of life, and safety within 60 days of surgery. Final analysis included 517 patients enrolled between May 2011 and May 2021; of the total, 207 were randomized to the HIPECgroup, and 208 were randomized to the control group. Baseline characteristics were not significantly different. Com paring the HIPEC group to controls, median OS was 54.3 versus 45.8 months (hazard ratio, 0.73; 95% confidence interval, 0.56-0.96). Progression-free survival had a reported hazard ratio of 0.79 comparing HIPEC to controls (95% confidence in terval, 0.63-0.99), and median progression free survival was 10.2 months with HIPEC and 9.5 months without. Results were consistent across subgroups, and there were nosignificant interactions between treatment effect and any patient or tumor char acteristics. Sensitivity analyses additionally showed similar results. The most common adverse events included anemia, electrolyte disturbance, hepatotoxicity, and renal failure in the HIPEC group and anemia in the control group. In the HIPEC group, 35 individuals required red blood cell transfusions, compared with 19 in the control group. These results indicate a statistically significant overall benefit of HIPEC treatment in the first recurrence of ovarian cancer, benefitting both overall and progression-free survival. There were significantly more adverse events associated with HIPEC, but these did not impact overall patient-reported outcomes. This is the first study of its kind to evaluate HIPEC in association with recurrent ovarian cancers.