Hyperthermic intraperitoneal chemotherapy for recurrent ovarian cancer (CHIPOR): a randomised, open-label, phase 3 trial - 14/11/24

Doi : 10.1016/S1470-2045(24)00531-X

Jean-Marc Classe, ProfMD ^a,^b,⁎ , Pierre Meeus, MD ^c, Delphine Hudry, MD ^d, Romuald Wernert, MD ^e, François Quenet, MD ^f, Frédéric Marchal, ProfMD ^g, Gilles Houvenaeghel, ProfMD ^h, Anne-Sophie Bats, MD ⁱ, Fabrice Lecuru, ProfMD ^i,^{^{†
Current affiliation: Institut Curie, Paris, France}}, Gwenaël Ferron, MD ^j, Cécile Brigand, ProfMD ^k, Dominique Berton, MD ^a, Laurence Gladieff, MD ^j, Florence Joly, ProfMD ^l,^m, Isabelle Ray-Coquard, MD ^c, Sylvaine Durand-Fontanier, MD ⁿ, Gabriel Liberale, MD ^o, Marc Pocard, ProfMD ^p,^q, Constantin Georgeac, MD ^r, Sébastien Gouy, MD ^s,^t, Jean-Marc Guilloit, MD ^l, Frédéric Guyon, MD ^u, Cristina Costan, MD ^v, Jean-Marc Rousselet, MD ^w, Lara de Guerké, MD ^x, Naoual Bakrin, MD ^y,^z, Emilie Brument, MSc ^aa, Elodie Martin, MSc ^a, Bernard Asselain, MD ^ab, Loïc Campion, MD ^a,^b, Olivier Glehen, ProfMD ^y,^z
for the
UNICANCER/CHIPOR Investigators^*
Investigators are listed in the Supplementary Material
^a Institut de Cancérologie de L’Ouest, Saint Herblain, France
^b Nantes Université, INSERM 1307, CNRS 6075, Université d’Angers, CRCI2NA, Nantes, France
^c Centre Léon Bérard and University Claude Bernard, Lyon, France
^d Centre Oscar Lambret, Lille, France
^e Institut de Cancérologie de L’Ouest, Angers, France
^f ICM Val d’Aurelle, Montpellier, France
^g Institut de Cancérologie de Lorraine, Vandoeuvre-Lès-Nancy, France
^h Aix-Marseille University CNRS, INSERM, Institut Paoli-Calmettes, Department of Surgical Oncology, CRCM, Marseille, France
ⁱ Hôpital Européen Georges-Pompidou, APHP-Centre Université Paris Cité, Paris, France
^j Oncopole CLAUDIUS REGAUD, IUCT-Oncopole, Toulouse, France
^k CHU Hautepierre, Strasbourg, France
^l Centre François Baclesse, Caen, France
^m University Caen Normandy, Caen, France
ⁿ CHU Dupuytren, CNRS UMR 7252, Limoges, France
^o Institut Jules Bordet, Hôpitaux Universitaires de Bruxelles, Bruxelles, Belgium
^p Université Paris Cité, INSERM, U1275 CAP Paris-Tech, Paris, France
^q Department of Digestive, Hepatobiliary Surgery and Liver Transplantation, Pitié-Salpêtrière Hospital, Assistance Publique–Hôpitaux de Paris, Paris, France
^r Centre Médico-Chirurgical de la Sarthe, Le Mans, France
^s Department of Gynecological Surgery, INSERM Unit 10–30, Gustave Roussy Cancer Campus, Villejuif, France
^t University Paris-Saclay, Gif-sur-Yvette, France
^u Institut Bergonié, CLCC Bordeaux Nouvelle Aquitaine, Bordeaux, France
^v CHU Grenoble Alpes, Grenoble, France
^w CHU Dijon, Dijon, France
^x Hôpital Maisonneuve-Rosemont CIUSSSEMTL–Université de Montréal, Montreal, QC, Canada
^y Centre Hospitalier Lyon Sud, Pierre-Bénite, France
^z CICLY, Université Lyon 1, Lyon, France
^aa UCGI, Prodige Intergroup, UNICANCER, Paris, France
^ab ARCAGY-GINECO, Paris, France

^*Correspondence to: Prof Jean-Marc Classe, Department of Oncologic Surgery, Institut de Cancérologie de l’Ouest, 44805 Saint Herblain, FranceDepartment of Oncologic SurgeryInstitut de Cancérologie de l’OuestSaint Herblain44805France

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Summary

Background

Hyperthermic intraperitoneal chemotherapy (HIPEC) at interval cytoreductive surgery for ovarian cancer improves overall survival but its role in recurrent disease is uncertain. We aimed to compare outcomes in patients treated with or without HIPEC during surgery for recurrent ovarian cancer.

Methods

The multicentre, open-label, randomised, phase 3 CHIPOR trial was conducted at 31 sites in France, Belgium, Spain, and Canada, and enrolled patients with first relapse of epithelial ovarian cancer at least 6 months after completing platinum-based chemotherapy. Eligible patients were aged 18 years or older with WHO performance status of less than 2. After six cycles of platinum-based chemotherapy (and optional bevacizumab), patients amenable to complete cytoreductive surgery were randomly assigned centrally in a 1:1 ratio, using a web-based system and a minimisation procedure, during surgery to receive HIPEC (cisplatin 75 mg/m² in 2 L/m² of serum at 41±1°C for 60 min) or not, stratified by centre, completeness of cytoreduction score, platinum-free interval, and latterly, planned poly(ADP-ribose) polymerase inhibitor use. The primary endpoint was overall survival, analysed on an intention-to-treat basis in all randomly assigned patients. This ongoing trial is registered with ClinicalTrials.gov, NCT01376752.

Findings

Between May 11, 2011, and May 14, 2021, 415 female patients were randomly assigned (207 HIPEC, 208 no HIPEC). At the primary analysis (median follow-up 6·2 years, IQR 4·1–8·1), 268 (65%) patients had died (126 [61%] of 207 in the HIPEC group; 142 [68%] of 208 in the no-HIPEC group). Overall survival was significantly improved with HIPEC (stratified hazard ratio 0·73, 95% CI 0·56–0·96; p=0·024). Median overall survival was 54·3 months (95% CI 41·9–61·7) with HIPEC versus 45·8 months (38·9–54·2) without. Grade 3 or worse adverse events within 60 days after surgery occurred in 102 (49%) of 207 patients receiving HIPEC versus 56 (27%) of 208 receiving no HIPEC, the most common being anaemia (47 [23%] vs 30 [14%]), hepatotoxicity (23 [11%] vs 18 [9%]), electrolyte disturbance (28 [14%] vs two [1%]), and renal failure (20 [10%] vs three [1%]). There were three deaths within 60 days of surgery, all in the no-HIPEC group.

Interpretation

Adding HIPEC to cytoreductive surgery after response to platinum-based chemotherapy at first epithelial ovarian cancer recurrence significantly improved overall survival. When treating patients with late first relapse of high-grade serous or high-grade endometrioid ovarian cancer amenable to complete cytoreductive surgery at specialist centres, platinum-based HIPEC should be considered to extend overall survival.