The final survival analysis of the Dutch-Belgian phase III OVHIPEC-1 trial showed that the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery was associated with maintained progression-free and overall survival benefits at 10 years in women with advanced ovarian cancer considered ineligible for primary complete cytoreduction. The study was reported in The Lancet Oncology by lead author Lot Aronson, MD, and senior author Willemien J. van Driel, MD, PhD, both of the Department of Gynecologic Oncology, Netherlands Cancer Institute, and colleagues.1
Lot Aronson, MD
Willemien J. van Driel, MD, PhD
Study Details
In the open-label trial, 245 patients with primary epithelial International Federation of Gynecology and Obstetrics (FIGO) stage III ovarian cancer from eight HIPEC centers in the Netherlands and Belgium were randomly assigned between April 2007 and April 2016 to receive interval cytoreductive surgery plus HIPEC with cisplatin at 100 mg/m2 for 90 minutes (n = 122) or interval cytoreductive surgery alone (n = 123). All patients had extensive disease and were not considered eligible for primary cytoreduction. In addition, they had not experienced disease progression during at least three cycles of neoadjuvant carboplatin AUC 5 plus paclitaxel at 175 mg/m2 given every 3 weeks.
Stratification factors included prior suboptimal cytoreductive surgery and the number of abdominal regions involved. Analysis of progression-free and overall survival was performed in the intention-to-treat population. In an analysis at 4.7 years of follow-up, the HIPEC group had significantly better progression-free and overall survival.
Survival Outcomes
The median follow-up at the time of final analysis was 10.4 years (95% confidence interval [CI] = 9.5–13.3 years) in the surgery/HIPEC group and 10.1 years (95% CI = 8.4–12.9 years) in the surgery-alone group. The median number of cycles of adjuvant chemotherapy received after surgery was 0 in 4% vs 6%, 1 in 0% vs 2%, 2 in 2% vs 2%, and 3 in 94% vs 91% of patients, respectively.
Median progression-free survival was 14.3 months (95% CI = 12.0–18.5 months) with surgery/HIPEC vs 10.7 months (95% CI = 9.6–12.0 months) with surgery alone (hazard ratio [HR] = 0.63, 95% CI = 0.48–0.83, P = .0008). Rates at 5 and 10 years were 12.3% vs 6.6% and 10.1% vs 6.6%.
For stratification factors in the surgery/HIPEC group vs the surgery-alone group, median progression-free survival was 28.9 vs 12.3 months among 12 vs 12 patients with prior suboptimal cytoreductive surgery (HR = 0.48, 95% CI = 0.15–1.55) and 14.1 vs 10.6 months among 110 vs 111 patients with no prior suboptimal cytoreductive surgery (HR = 0.69, 95% CI = 0.49–1.00); progression-free survival was 17.7 vs 11.5 months among 83 vs 83 patients with zero to five involved abdominal regions (HR = 0.65, 95% CI = 0.42–1.00) and 9.9 vs 8.2 months among 39 vs 40 patients with six to eight involved abdominal regions (HR = 0.60, 95% CI = 0.32–1.12). In other subgroups, hazard ratios were 0.60 (95% CI = 0.33–1.08) among 88 patients aged 65 and older, 0.71 (95% CI = 0.46–1.10) among 157 patients up to age 65, 0.69 (95% CI = 0.48–0.99) among 219 patients with high-grade serous histology, and 0.57 (95% CI = 0.18–1.84) among 24 patients with other histologic types.
Subsequent anticancer therapy was received by 105 patients in the surgery/HIPEC group and 110 patients in the surgery-alone group. The most common treatments in both groups were platinum-based chemotherapy (84% and 80%), nonplatinum-based chemotherapy (44% and 53%), and targeted therapies (32% and 40%; bevacizumab in 22% and 27%). Radiotherapy was given to 15% of patients in each group receiving subsequent therapy.
Median overall survival was 44.9 months (95% CI = 38.6–55.1 months) with surgery/HIPEC vs 33.3 months (95% CI = 29.0–39.1 months) with surgery alone (HR = 0.70, 95% CI = 0.53–0.92, P = .011). Rates at 5 and 10 years were 36.9% vs 19.7% and 16.1% vs 10.9%, respectively. For stratification factors in the surgery/HIPEC group vs surgery-alone group, median overall survival was 63.0 vs 44.1 months among patients with prior suboptimal cytoreductive surgery (HR = 0.59, 95% CI = 0.18–1.91) and 42.2 vs 33.3 months among those with no prior suboptimal cytoreductive surgery (HR = 0.72, 95% CI = 0.49–1.05); median overall survival was 57.0 vs 37.0 months among patients with zero to five involved abdominal regions (HR = 0.65, 95% CI = 0.41–1.02) and 31.0 vs 27.3 months among those with six to eight involved abdominal regions (HR = 0.82, 95% CI = 0.45–1.48). In other subgroups, hazard ratios were 0.62 (95% CI = 0.34–1.14) among patients aged 65 and older, 0.77 (95% CI = 0.49–1.21) among those up to age 65, 0.75 (95% CI = 0.51–1.09) among patients with high-grade serous histology, and 0.44 (95% CI = 0.13–1.47) among those with other histologic types.
The investigators concluded: “This updated 10-year survival analysis from the OVHIPEC-1 trial confirms the significant improvement in progression-free and overall survival with the addition of HIPEC to interval cytoreductive surgery in patients with FIGO stage III ovarian cancer with extensive disease for whom primary complete cytoreduction is not considered feasible.”
DISCLOSURE: The study was funded by the Dutch Cancer Foundation. For full disclosures of the study authors, visit thelancet.com.
REFERENCE
1. Aronson SL, Lopez-Yurda M, Koole SN, et al: 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. Lancet Oncol 24:1109-1118, 2023.
