Cytoreductive Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy in Patients With Advanced Ovarian Cancer (OVHIPEC-1): Final Survival Analysis of a Randomised, Controlled, Phase 3 Trial

Abstract

Although the 5-year survival of patients with advanced ovarian cancer has improved, overall survival at 10 years remains approximately 13%. Hyperthermic intraperitoneal chemotherapy (HIPEC) involves the delivery of chemotherapeutic agents directly into the peritoneum in combination with hyperthermia, which enhances penetration and increases sensitivity to platinum compounds by inducing a transient state of homologous recombination deficiency. The initial analysis of the OVHPIEC-1 trial showed that addition of HIPEC to interval cytoreductive surgery had benefit in stage III epithelial ovarian cancer, with an improvement in progression-free and overall survival compared with cytoreductive surgery alone at 4.7 years of follow-up in patients ineligible for primary cytoreduction; however, long-term survival outcomes are crucial to inform guidelines for the management of this disease. This updated survival analysis reports on the final survival outcomes after 10 years of follow-up in the OVHIPEC-1 trial, a multicenter, open-label, randomized, controlled, phase 3 trial to evaluate interval cytoreductive surgery in patients with stage III epithelial ovarian cancer. Patients aged 18–76 years with histologically confirmed FIGO stage III epithelial ovarian, fallopian tube, or peritoneal cancer that had not progressed during treatment with neoadjuvant carboplatin and paclitaxel were eligible. Participants were randomized (1:1) to interval cytoreductive surgery either without HIPEC (surgery group) or with HIPEC. The primary end point was progression-free survival, defined as time from randomization to disease recurrence, progression, or death from any cause. A total of 245 patients were randomized to surgery alone (n = 123) or surgery plus HIPEC (n = 122) between April 1, 2007, and April 30, 2016. The data cutoff was March 31, 2022, with a median follow-up time of 10.1 years (95% confidence interval [CI], 8.4–12.9) in the surgery group and 10.4 years (95% CI, 9.5–13.3) in the surgery plus HIPEC group. Intention-to-treat analysis found that 114 (93%) of 123 patients in the surgery group had an event of disease recurrence or progression (n = 110) or death (n = 4), and 109 (89%) of 122 patients in the surgery plus HIPEC group had an event of disease recurrence or progression (n = 105) or death (n = 4). The median progression-free survival was 10.7 months (95% CI, 9.6–12.0) in the surgery group and 14.3 months (95% CI, 12.0–18.5) in the surgery plus HIPEC group (hazards ratio, 0.63; 95% CI, 0.48–0.83; stratified log-rank P = 0.0008). This updated 10-year survival analysis of the OVHPIEC-1 trial represents the longest follow-up survival data from a randomized trial of HIPEC in primary ovarian cancer and confirms the significant improvement in progression-free and overall survival compared with surgery alone among patients with stage III ovarian cancer.