HIPEC Improves Overall Survival in Recurrent Ovarian Cancer: Results from the Phase 3 CHIPOR Trial

A recent trial found that Hyperthermic intraperitoneal chemotherapy (HIPEC) in addition to cytoreductive surgery has significantly improved the overall survival rates for recurrent ovarian cancer. The trial results are published in the journal The Lancet Oncology.

Ovarian cancer is the leading cause of cancerous death in women. platinum-based chemotherapy and complete cytoreductive surgery, with bevacizumab or maintenance poly (ADP-ribose) polymerase (PARP) inhibitor (or both), are the standard treatments for primary diagnosis and at first platinum-sensitive relapse depending on clinical and tumor characteristics. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a single intraoperative procedure that delivers chemotherapy in a heated solution directly into the abdominal cavity after cytoreductive surgery. Previous trials showed that HIPEC improved both overall survival and progression-free survival when used as primary treatment for advanced epithelial ovarian cancer during interval cytoreductive surgery. As later trials gave ambiguous results researchers conducted a trial to evaluate platinum-based chemotherapy followed by complete cytoreductive surgery with or without HIPEC, for the first relapse of ovarian cancer.

The multicentre, open-label, randomized, phase 3 CHIPOR trial was conducted at 31 sites in France, Belgium, Spain, and Canada. The trial enrolled patients with the first relapse of epithelial ovarian cancer at least 6 months after completing platinum-based chemotherapy. Individuals aged 18 years or older with WHO performance status of less than 2 were enrolled in the trial. After six cycles of platinum-based chemotherapy (and optional bevacizumab), patients suitable for cytoreductive surgery were randomly assigned centrally in a 1:1 ratio, using a web-based system and a minimization procedure. The participants were randomized to receive HIPEC (cisplatin 75 mg/m² in 2 L/m² of serum at 41±1°C for 60 min) during surgery, based on the center, completeness of cytoreduction score, platinum-free interval, and latterly, planned poly (ADP-ribose) polymerase inhibitor use. The primary endpoint was overall survival, analyzed on an intention-to-treat basis for all randomized individuals.

Findings:

• About 415 female patients were randomly assigned with 207 receiving HIPEC and 208 not receiving HIPEC.

• At the primary analysis, 268 (65%) patients had died (126 [61%] of 207 in the HIPEC group; 142 [68%] of 208 in the no-HIPEC group).

• HIPEC significantly improved the Overall survival (stratified hazard ratio 0·73, 95% CI 0·56–0·96; p=0·024).

• Median overall survival was 54·3 months with HIPEC versus 45·8 months without.

• Grade 3 or worse adverse events within 60 days after surgery occurred in 102 (49%) of 207 patients receiving HIPEC versus 56 (27%) of 208 receiving no HIPEC.

• Among the adverse events the most common are anemia (23% vs 14%), hepatotoxicity (11% vs 9%), electrolyte disturbance (14%] vs 1%), and renal failure (10% vs three 1%).

• There were three deaths within 60 days of surgery, all in the no-HIPEC group.

Thus, the study concluded that adding HIPEC to cytoreductive surgery significantly improved the overall survival in recurrent epithelial cancer. Despite the presence of adverse effects, HIPEC can be used to improve the survival rate in individuals with ovarian cancer relapse.

Further reading:

Classe JM, Meeus P, Hudry D, et al. Hyperthermic intraperitoneal chemotherapy for recurrent ovarian cancer (CHIPOR): a randomised, open-label, phase 3 trial. Lancet Oncol. Published online November 13, 2024. doi:10.1016/S1470-2045(24)00531-X.