Postoperative Hepatic Arterial Infusion With Oxaliplatin After Surgery of Four or More Colorectal Liver Metastases: A Randomized Phase II Trial

Author(s): Maximiliano Gelli, MD, PhD¹; Jacques Ewald, MD²; Marie-Laure Tanguy, MD^3,4; Guillaume Passot, MD, PhD⁵; Francois Quenet, MD, PhD⁶; Yann Touchefeu, MD, PhD⁷; Hélène Senellart, MD⁸; Fabrice Muscari, MD, PhD⁹; Astrid Lievre, MD, PhD¹⁰; René Adam, MD, PhD¹¹; Lambros Tselikas, MD, PhD¹; Thomas Aparicio, MD, PhD¹²; Julien Taieb, MD, PhD¹³; Charles Mastier, MD¹⁴; Jean-Marc Regimbeau, MD, PhD¹⁵; Amani Asnacios Lecerf, MD¹⁶; David Tougeron, MD, PhD¹⁷; Valerie Boige, MD, PhD¹⁸; Thierry De Baere, MD, PhD¹; David Malka, MD, PhD¹⁹; Diane Goéré, MD, PhD²⁰;

Source: DOI: 10.1200/JCO-25-01737

Dr. Anjan Patel's Thoughts

For high-risk patients with four or more colorectal liver metastases, adjuvant hepatic arterial infusion oxaliplatin roughly doubled hepatic recurrence-free survival versus standard IV chemotherapy (25 vs. 12 months), with recurrence-free survival (RFS) benefit as well. Overall survival (OS) didn't reach significance but the absolute difference and 5-year OS of 62% versus 47% suggest a real effect worth confirming in phase III. Toxicity was higher in the hepatic arterial infusion (HAI) arm but manageable with no treatment-related deaths. Generalizability remains the challenge, these needs specialized centers with HAI expertise, but worth keeping in mind for your highest-risk resected liver met patients.

PURPOSE

To evaluate the efficacy and safety of adjuvant hepatic arterial infusion (HAI) of oxaliplatin combined with intravenous (IV) fluorouracil/leucovorin (LV5FU2) after curative-intent surgery of ≥4 colorectal liver metastases (CRLM).

METHODS

Patients with an Eastern Cooperative Oncology Group performance status 0-1, who underwent resection or ablation of ≥4 CRLM after preoperative IV chemotherapy were enrolled. Patients were randomly assigned (1:1) to receive adjuvant oxaliplatin via HAI (HAI group, n = 50) or IV infusion (IV group, n = 49), both combined with IV LV5FU2 for least 3 months. The primary end point was hepatic recurrence-free survival (h-RFS). Secondary end points included RFS, overall survival (OS), safety, and feasibility.

RESULTS

After a median follow-up of 59 months (IQR, 45-71), the median h-RFS was 25 (95% CI, 16 to 37) months in the HAI group versus 12 (95% CI, 8 to 19) months in the IV group (hazard ratio [HR], 0.63 [95% CI, 0.40 to 0.99]; P = .047). Median RFS was 14 months (95% CI, 10 to 20) in the HAI group versus 9 months (95% CI, 7 to 11) in the IV group (HR, 0.63 [95% CI, 0.41 to 0.97]; P = .03). Median OS was 74 months (95% CI, 51 to not defined) in the HAI group versus 57 months (95% CI, 37 to 69) in the IV group (HR, 0.61 [95% CI, 0.33 to 1.12]; P = .11). Five-year OS was 62% in the HAI arm compared with 47% in the IV arm. Grade 3 to 4 adverse events occurred in 58% of HAI patients and 32% of IV patients (P = .02). No treatment-related deaths were reported. Four or more cycles of adjuvant chemotherapy were delivered in 81% of patients in the HAI group and 78% in the IV group (P = .75).

CONCLUSION

Adjuvant oxaliplatin HAI plus LV5FU2 improves h-RFS after curative-intent surgery of CRLM in high-risk patients, with an acceptable safety profile. These results support further evaluation in a phase III trial.

Author Affiliations

¹Department of Anaesthesia, Surgery and Interventional Radiology, Gustave Roussy Hospital, University of Paris-Saclay, Villejuif, France; ²Department of Surgery, Paoli-Calmettes Institute, Marseille, France; ³Department of Biostatistics and Epidemiology, Gustave Roussy, Université Paris Saclay, Villejuif, France; ⁴Oncostat U1018, Inserm, University Paris-Saclay, Labeled Ligue Contre le Cancer, Villejuif, France; ⁵Department of Surgical Oncology, University Hospital Lyon Sud, Pierre Bénite, France; ⁶Department of Surgical Oncology, Institut Régional du Cancer de Montpellier, Montpellier, France; ⁷Department of Hepato-Gastroenterology, Institut des Maladies de l’Appareil Digestif, University Hospital Nantes, France; ⁸Department of Medical Oncology, Institut de Cancérologie de l’Ouest, Centre René Gauducheau, Saint-Herblain, France; ⁹Department of Digestive Surgery, Hôpital Rangueil, University Hospitals Toulouse, Toulouse, France; ¹⁰Department of Gastroenterology, University Hospital, Rennes, France; ¹¹Department of Hepatobiliary Surgery and Transplantation, AP-HP Hôpital Paul-Brousse, University of Paris-Saclay, Villejuif, France; ¹²Gastroenterology and Digestive Oncology Department, CHU Saint Louis, APHP, Université de Paris, Paris, France; ¹³Department of Gastroenterology and Digestive Oncology, AP-HP Hôpital Européen Georges Pompidou, Paris, France; ¹⁴Interventional Radiology Department, CLCC Léon Bérard, Lyon, France; ¹⁵Department of Oncology and Digestive Surgery, CHU Amiens-Picardie, Amiens, France; ¹⁶Department of Medical Oncology, Curie Institute, Saint-Cloud, France; ¹⁷Department of Hepatogastroenterology, Poitiers University Hospital, Poitiers, France; ¹⁸Department of Cancer Medicine, Gustave Roussy, University of Paris-Saclay, Villejuif, France; ¹⁹Department of Medical Oncology, Institut Mutualiste Montsouris, Paris, France; ²⁰Department of Surgical Oncology, University Hospital Saint-Louis, Assistance Publique–Hôpitaux de Paris, Paris, France

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