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

Author(s): S Lot Aronson, MD^1,2; Marta Lopez-Yurda, PhD³; Simone N Koole, MD PhD^1,2; Prof Jules H Schagen van Leeuwen, MD PhD⁴; Hendrik W R Schreuder, MD PhD⁵; Ralph H M Hermans, MD PhD⁶; Prof Ignace H J T de Hingh, MD PhD^7,8; Mignon D J M van Gent, MD PhD^9,10; Henriëtte J G Arts, MD PhD¹¹; Maaike A P C van Ham, MD PhD¹²; Prof Peter A van Dam, MD PhD¹³; Peter Vuylsteke, MD^14,15; Arend G J Aalbers, MD¹⁶; Victor J Verwaal, MD PhD¹⁷; Prof Koen K Van de Vijver, MD PhD¹⁸; Prof Neil K Aaronson, PhD¹⁹; Prof Gabe S Sonke, MD PhD²⁰; Willemien J van Driel, MD PhD^1,2

Source: doi.org/10.1016/S1470-2045(23)00396-0

Dr. Anjan Patel's Thoughts

The final results from the OVHIPEC1 study confirm a survival benefit in stage III epithelial ovarian cancers. The OS benefit was about 12 months, and the PFS benefit was four months in favor of CRS + HIPEC compared to CRS alone. This should be offered to patients in the context of definitive surgery.

BACKGROUND

The OVHIPEC-1 trial previously showed that the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery resulted in improved progression-free and overall survival compared with cytoreductive surgery alone at 4·7 years of follow-up in patients with stage III epithelial ovarian cancer who were ineligible for primary cytoreduction. We report the final survival outcomes after 10 years of follow-up.

METHODS

In this open-label, randomised, controlled, phase 3 trial, patients with primary epithelial stage III ovarian cancer were recruited at eight HIPEC centres in the Netherlands and Belgium. Patients were eligible if they were aged 18–76 years, had not progressed during at least three cycles of neoadjuvant carboplatin plus paclitaxel, had a WHO performance status score of 0–2, normal blood counts, and adequate renal function. Patients were randomly assigned (1:1) to undergo interval cytoreductive surgery without HIPEC (surgery group) or with HIPEC (100 mg/m2 cisplatin; surgery-plus-HIPEC group). Randomisation was done centrally by minimisation with a masked web-based allocation procedure at the time of surgery when residual disease smaller than 10 mm diameter was anticipated, and was stratified by institution, previous suboptimal cytoreductive surgery, and number of abdominal regions involved. The primary endpoint was progression-free survival and a secondary endpoint was overall survival, analysed in the intention-to-treat population (ie, all randomly assigned patients). This study is registered with ClinicalTrials.gov, NCT00426257, and is closed.

FINDINGS

Between April 1, 2007, and April 30, 2016, 245 patients were enrolled and followed up for a median of 10·1 years (95% CI 8·4–12·9) in the surgery group (n=123) and 10·4 years (95% CI 9·5–13·3) in the surgery-plus-HIPEC group (n=122). Recurrence, progression, or death occurred in 114 (93%) patients in the surgery group (median progression-free survival 10·7 months [95% CI 9·6–12·0]) and 109 (89%) patients in the surgery-plus-HIPEC group (14·3 months [12·0–18·5]; hazard ratio [HR] 0·63 [95% CI 0·48–0·83], stratified log-rank p=0·0008). Death occurred in 108 (88%) patients in the surgery group (median overall survival 33·3 months [95% CI 29·0–39·1]) and 100 (82%) patients in the surgery-plus-HIPEC group (44·9 months [95% CI 38·6–55·1]; HR 0·70 [95% CI 0·53–0·92], stratified log-rank p=0·011).

INTERPRETATION

These updated survival results confirm the long-term survival benefit of HIPEC in patients with primary stage III epithelial ovarian cancer undergoing interval cytoreductive surgery.

FUNDING

Dutch Cancer Foundation (KWF Kankerbestrijding).

Author Affiliations

¹Department of Gynecologic Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands; ²Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands; ³Department of Biometrics, Netherlands Cancer Institute, Amsterdam, Netherlands; ⁴Department of Obstetrics and Gynecology, Sint Antonius Hospital, Nieuwegein, Netherlands; ⁵Department of Gynecologic Oncology, UMC Utrecht Cancer Center, Utrecht, Netherlands; ⁶Department of Gynecology and Obstetrics, Catharina Hospital, Eindhoven, Netherlands; ⁷Department of Surgery, Catharina Hospital, Eindhoven, Netherlands; ⁸Department of Epidemiology, GROW-School for Oncology Reproduction, Maastricht University, Maastricht, Netherlands; ⁹Department of Obstetrics and Gynecology, Amsterdam University Medical Center, Amsterdam, Netherlands; ¹⁰Center for Gynecologic Oncology Amsterdam, Amsterdam, Netherlands; ¹¹Department of Gynecologic Oncology, University Medical Center Groningen, Groningen, Netherlands; ¹²Department of Gynecologic Oncology, Radboud University Medical Centre, Nijmegen, Netherlands; ¹³Department of Gynecologic Oncology, University Hospital Antwerp, Antwerp, Belgium; ¹⁴Department of Medical Oncology, UCL Louvain, CHU Namur Sainte-Elisabeth, Namur, Belgium; ¹⁵Department of Internal Medicine, University of Botswana, Gaborone, Botswana; ¹⁶Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands; ¹⁷Department of Surgery, Skåne University Hospital, Malmö, Sweden; ¹⁸Department of Pathology, Ghent University Hospital, Ghent, Belgium; ¹⁹Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, Netherlands; ²⁰Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands

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