Adding HIPEC Boosts Survival in Recurrent Ovarian Cancer

Adding hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery significantly improved overall survival (OS) in women with platinum-sensitive, recurrent epithelial ovarian carcinoma, a phase III randomized trial showed.

In over 400 women at first epithelial ovarian cancer recurrence, those who received HIPEC had a median OS of 54.3 months compared with 45.8 months for those who did not (HR 0.73, 95% CI 0.56-0.96, P=0.024), reported Jean-Marc Classe, MD, of the Institut de Cancérologie de l’Ouest in Saint Herblain, France, and colleagues.

The 5-year OS rates were 46% in the HIPEC group versus 38% in the no-HIPEC group, they noted in Lancet Oncology.

The trial “provides the first prospective randomized evidence showing the benefit of HIPEC in patients undergoing complete cytoreductive surgery for the first late relapse (treatment-free interval of at least 6 months since last platinum-based chemotherapy) of ovarian cancer,” wrote Classe and colleagues.

“When treating patients with late first relapse of serous or high-grade endometrioid ovarian cancer amenable to complete cytoreductive surgery, platinum-based HIPEC administered in specialist centers should be considered following neoadjuvant chemotherapy,” they added.

In a comment accompanying the study, Taymaa May, MD, MSc, of Brigham and Women’s Hospital and Harvard Medical School in Boston, noted that “these promising results could signal a paradigm shift in the role of secondary cytoreductive surgery for ovarian carcinoma. As the landscape of ovarian cancer management evolves, HIPEC is poised to be an integral component of multimodal therapeutic strategies aimed at improving long-term outcomes.”

The progression-free survival (PFS) benefit seen in the trial was more modest, with a median PFS of 10.2 months with HIPEC and 9.5 months without HIPEC (HR 0.79, 95% CI 0.63-0.99). The median peritoneal PFS was 12.3 months and 12.1 months, respectively (HR 0.74, 95% CI 0.57-0.94).

“This observation is particularly important as peritoneal carcinomatosis and progression are often associated with increased mortality,” May observed.

The objective of HIPEC — a single intraoperative procedure that delivers chemotherapy in a heated solution directly into the abdominal cavity after cytoreductive surgery — “is to improve the treatment of peritoneal microscopic residual disease, adding the effects of thermal shock, increased chemotherapy penetration at the peritoneal surface, and increased cancer sensitivity to chemotherapy,” the researchers explained.

In the previous OVHIPEC-1 trial, HIPEC improved both OS and PFS as primary treatment in patients undergoing interval cytoreductive surgery following neoadjuvant chemotherapy as compared with no HIPEC. However, Classe and colleagues noted that the role of HIPEC in other settings — including the recurrent setting — has been less clear.

The current trial, known as CHIPOR, was conducted at 31 sites in France, Belgium, Spain, and Canada, and included patients with a WHO performance status of less than 2, who had experienced a first relapse of epithelial ovarian cancer at least 6 months after completing six cycles of platinum-based chemotherapy.

Between May 2011 and May 2021, 415 patients were randomly assigned to the HIPEC group (cisplatin 75 mg/m² in 2 L/m² of serum at 41±1°C for 60 minutes) or the no-HIPEC group. Mean patient age in the HIPEC group was 62, and 73% had high-grade serous disease. In the no-HIPEC group, mean age was 59, and 76% had high-grade serous disease. In both groups, 60% of patients were negative for BRCA.

At a median follow-up of 6.2 years, 61% of patients in the HIPEC group and 68% of those in the no-HIPEC group had died.

Within the first 60 days after surgery, grade ≥3 adverse events (AEs) occurred in 49% of patients receiving HIPEC versus 27% of those in the no-HIPEC group. The most common AEs were anemia (23% vs 14%), hepatotoxicity (11% vs 9%), electrolyte disturbance (14% vs 1%), and renal failure (10% vs 1%).

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

As for study limitations, Classe and colleagues noted that they had assumed a median OS of 29 months in the control group, based on the ICON4 trial — much shorter than the reported median OS of 45.8 months.

Acknowledging that this was a potential “weakness limiting interpretation,” the authors said the longer OS was due to the trial’s long duration of enrollment and follow-up, during which treatment options, lifestyle changes, and improved anesthesiology led to improvements in prognosis.

May also noted that the study’s protocol differed from other second-line surgical studies in which secondary cytoreductive surgery was performed before adjuvant chemotherapy. In this study, patients received up to six cycles of a platinum-based chemotherapy doublet before secondary cytoreductive surgery.

“Although the CHIPOR trial raises questions about the optimal therapeutic sequence in recurrent ovarian carcinoma, it demonstrates a clear survival advantage in this patient population and presents an important treatment option for patients with this disease,” May wrote.