Hyperthermic intraperitoneal chemotherapy in platinum-sensitive relapsed epithelial ovarian cancer: The CHIPOR randomized phase III trial.

Jean-Marc Classe Institut de Cancérologie Ouest, Nantes, France info_outline Jean-Marc Classe, Pierre Meeus, Eric Leblanc, Romuald Wernert, Francois Quenet, Frédéric Marchal, Gilles Houvenaeghel, Anne-Sophie Bats, Gwenael Ferron, Cecile Brigand, Dominique Berton, Laurence Gladieff, Florence Joly, Isabelle Laure Ray-Coquard, Sylvaine Durand-Fontanier, Gabriel Liberale, Emilie Brument, Bernard Asselain, Loic Campion, Olivier Glehen

Authors Jean-Marc Classe Institut de Cancérologie Ouest, Nantes, France info_outline Jean-Marc Classe, Pierre Meeus, Eric Leblanc, Romuald Wernert, Francois Quenet, Frédéric Marchal, Gilles Houvenaeghel, Anne-Sophie Bats, Gwenael Ferron, Cecile Brigand, Dominique Berton, Laurence Gladieff, Florence Joly, Isabelle Laure Ray-Coquard, Sylvaine Durand-Fontanier, Gabriel Liberale, Emilie Brument, Bernard Asselain, Loic Campion, Olivier Glehen Organizations Institut de Cancérologie Ouest, Nantes, France, Centre Léon Bérard, Lyon, France, Centre Oscar Lambret, Lille, France, Centre Paul Papin, Angers, France, ICM Val d'Aurelle, Montpellier, France, Lorraine Cancer Institute, Vandoeuvre-Lès-Nancy, France, Institut Paoli Calmettes, Marseille, France, Hôpital Européen Georges Pompidou, Paris, France, Institut Claudius Regaud, IUCT-Oncopole, Toulouse, France, CHU Hautepierre, Strasbourg, France, Rene Gauducheau Cancer Center, Saint-Herblain, France, Francois Baclesse Cancer Center and GINECO, Caen, Paris, France, CHU Dupuytren, Limoges, France, Institut Jules Bordet, Bruxelles, Belgium, UCGI, Prodige Intergroup, UNICANCER, Paris, France, Arcagy-Gineco, Paris, France, ICO Cancer Center, CRCI2NA, UMR 1307 Inserm-UMR 6075 CNRS, Nantes, France, Lyon University hospital, Surgery department, Pierre-Bénite, France Abstract Disclosures Research Funding Other The trial was supported by R&D UNICANCER, by a Clinical Research Hospital Program grant from the French Ministry of Health/Institut National du Cancer and by French national Ligue against cancer Background: Standard treatment for patients with first platinum-sensitive relapse of epithelial ovarian cancer (EOC) is based on surgery and second-line systemic chemotherapy (CT). The role of hyperthermic intra-peritoneal chemotherapy (HIPEC) remains uncertain. Methods: The CHIPOR multicentric randomized phase III trial (NCT01376752), conducted in 31 institutions, enrolled patients with a first platinum-sensitive relapse (platinum-free interval of ≥6 months) of EOC. Patients were treated with 6 cycles of platinum and taxane based CT ± bevacizumab, and those amenable to a complete cytoreductive surgery at the end of CT were enrolled and randomly assigned to receive HIPEC (cisplatin 75 mg/m² at 41°C for 60 min) or not. Randomization was performed during complete cytoreductive surgery, stratified by center, surgical outcome (no residual disease vs residual <0.25 cm), chemotherapy-free interval before relapse, and PARP inhibitor use (yes vs no). The primary endpoint was overall survival (OS). The target sample size was 404 evaluable patients, providing 80% power at 5% alpha after 268 deaths. Secondary endpoints included progression-free survival (PFS), peritoneal PFS, patient-reported outcomes, safety, and postoperative morbidity and mortality (≤60 days after surgery). Results: Between May 11, 2011, and May 14, 2021, 415 patients were randomized. Baseline characteristics were balanced between treatment arms. At the data cutoff (Jan 8, 2023), with a median follow-up of 6.2 years, 268 patients (65%) had died. Efficacy results are summarized below. Conclusions: HIPEC significantly improves OS and peritoneal PFS of women with first platinum-sensitive relapse of EOC treated with second-line platinum-based CT followed by secondary complete cytoreductive surgery. Ongoing analyses, including patient reported outcome, BRCA status, bevacizumab exposure, and subsequent therapy, will be presented. Clinical trial information: NCT01376752. Endpoint HIPEC (n=207) No HIPEC (n=208) OS Events, n (%) 126 (61) 142 (68) Median, months (95% CI) 54.3 (41.9–61.7) 45.8 (39.9–54.2) HR (95% CI)* 0.69 (0.50–0.94), p=0.020 Global PFS Events, n (%) 180 (87) 184 (88) Median, months (95% CI) 10.2 (9.3–12.1) 9.8 (8.8–11.9) HR (95% CI)* 0.82 (0.64–1.06) Peritoneal PFS Events, n (%) 151 (73) 157 (75) Median, months (95% CI) 13.1 (10.7–16.3) 12.2 (9.8–13.1) HR (95% CI)* 0.71 (0.54–0.94) Postoperative adverse events, n (%) Grade 3/4 32 (15) 22 (11) Grade 3/4 renal toxicity 8 (4) 1 (<1) Grade 5 0 3 (1) Gastrointestinal stoma, n (%) 20 (10) 10 (5) *Stratified on stratification factors. HR = hazard ratio.