Based on results from the ongoing multicenter phase III CHIPOR trial, which were reported in The Lancet Oncology by Classe et al, the addition of hyperthermic intraperitoneal chemotherapy to complete cytoreductive surgery appeared to significantly improve overall survival in patients with platinum-sensitive late-relapsing epithelial ovarian cancer.
“These robust results … add to the recently reported OVHIPEC-1 trial, [which] demonstrated significantly improved overall survival with the adoption of hyperthermic intraperitoneal chemotherapy during interval cytoreductive surgery as primary treatment for advanced epithelial ovarian cancer,” the investigators remarked. “When treating patients with late first relapse of serous or high-grade endometrioid ovarian cancer [who are] amenable to complete cytoreductive surgery, platinum-based hyperthermic intraperitoneal chemotherapy administered in specialist centers should be considered following neoadjuvant chemotherapy.”
Study Details
The open-label CHIPOR trial, which is being conducted at 31 hospitals and cancer centers with high levels of surgical expertise across France, Belgium, Spain, and Canada, enrolled patients who presented with a first relapse of epithelial ovarian cancer at least 6 months after completing first-line platinum-based chemotherapy. They were required to be older than age 18 and have a World Health Organization performance status of less than 2.
Within 5 to 12 weeks of receiving six cycles of second-line platinum-based doublet chemotherapy and optional bevacizumab, a total of 415 eligible patients were randomly assigned in a 1:1 ratio to undergo complete cytoreductive surgery with (n = 207) or without (n = 208) hyperthermic intraperitoneal chemotherapy (60-minute infusion of 75 mg/m2 of cisplatin in 2 L/m2 of serum at 41ºC ± 1ºC). Stratification factors included the treatment center, outcome of cytoreductive surgery (measured by completeness of cytoreduction score; CC0 [no residual tumor] vs CC1 [residual tumor < 0.25 cm]), platinum-free interval (6 to ≤ 12 vs > 12 to ≤ 18 vs > 18 months), and, latterly, planned PARP inhibitor use after chemotherapy (yes vs no).
Overall survival in the intention-to-treat population was evaluated as the primary endpoint. Follow-up data were provided for a median of 6.2 years (interquartile range = 4.1–8.1 years).
Overall Survival
At the primary analysis, 61% and 68% of the patients who did and did not undergo hyperthermic intraperitoneal chemotherapy, respectively, had died. Hyperthermic intraperitoneal chemotherapy was found to significantly improve overall survival (stratified hazard ratio = 0.73, 95% confidence interval [CI] = 0.56–0.96; P = .024). The median duration of overall survival was longer with (54.3 months; 95% CI = 41.9–61.7 months) vs without (45.8 months; 95% CI = 38.9–54.2 months) hyperthermic intraperitoneal chemotherapy.
Adverse Events
Adverse events of grade 3 or higher were observed within 60 days after surgery in 49% of the patients who received hyperthermic intraperitoneal chemotherapy and 27% of those who did not. Anemia (23% vs 14%), hepatotoxicity (11% vs 9%), electrolyte disturbance (14% vs 1%), and renal failure (10% vs 1%) were among the most frequently reported events. Three patients died within 60 days of cytoreductive surgery, all of whom had undergone the procedure without hyperthermic intraperitoneal chemotherapy.
“CHIPOR provides robust evidence that hyperthermic intraperitoneal chemotherapy improves overall survival in patients undergoing complete cytoreductive surgery for platinum-sensitive recurrent ovarian cancer,” the investigators concluded. They furthermore stated: “Progression-free survival was improved, particularly peritoneal progression-free survival. Toxicity was increased with the use of hyperthermic intraperitoneal chemotherapy, and this treatment should be administered in specialist centers with experience in preventing and managing toxicities and with access to prophylactic thiosulfate. Nevertheless, there was no detectable detrimental effect on quality of life with hyperthermic intraperitoneal chemotherapy and no increase in pain in the immediate postoperative period.”
Jean-Marc Classe, MD, of Institut de Cancérologie de l'Ouest, Saint Herblain, France, is the corresponding author of the article in The Lancet Oncology.
Disclosure: The study was funded by the French National Cancer Institute and French League Against Cancer. For full disclosures of the study authors, visit thelancet.com.
