Induction triplet chemotherapy in patients with rectal adenocarcinoma and synchronous metastases, an AGEO-FFCD study.

Autor: Dabout V; Sorbonne University, Hepato-gastroenterology and digestive oncology department, Pitié Salpêtrière hospital, APHP, Paris, France., Mineur L; Department of Radiotherapy and Medical Oncology, Sainte-Catherine Institute, Avignon, France., Tougeron D; Department of Gastroenterology and Hepatology, Centre Hospitalo-universitaire de Poitiers, Poitiers, France., Malicot KL; Fédération Francophone de Cancérologie Digestive, Dijon, France., Gallois C; Department of Gastroenterology and Digestive Oncology, European Georges Pompidou hospital, Paris, France., Phelip JM; University Hospital of Saint Etienne, Saint Etienne, France; Unité HESPER EA-7425 Université Jean Monnet/Claude Bernard Lyon 1, France., Turpin A; Medical Oncology Department, University hospital, Lille, France and University of Lille, Lille, France., Cohen R; Sorbonne University, Department of Oncology, Saint-Antoine Hospital, INSERM 938, SIRIC CURAMUS, Paris, France., Demoustier B; Univ. Grenoble Alpes / Hepato-Gastroenterology and Digestive Oncology department, CHU Grenoble Alpes / Institute for Advanced Biosciences, CNRS UMR 5309-INSERM U1209, Grenoble, France., Hautefeuille V; Departments of Hepatogastroenterology and Digestive Oncology, CHU Amiens Picardie, Amiens, France., Locher C; Department of Hepato-gastroenterology and Digestive Oncology, Meaux Hospital, France., Levaché CB; Département d'Oncologie Médicale, Clinique Francheville, Périgueux, France., Mitry E; Medical Oncology department, Institut Paoli-Calmettes, Marseille, France., Lecomte T; Department of Hepatogastroenterology and Digestive Oncology, Hôpital Trousseau, CHRU de Tours, 37044 Tours Cedex 09; UMR INSERM U 1069, Université de Tours, 10 Boulevard Tonnellé, 37000, Tours, France., Brocard F; GINECO and Centre Oncologie de Gentilly, Nancy, France., Hassid D; Gastroenterology Department, AP-HP, Hôpital Saint-Louis/Lariboisière, Paris, France., Porte M; Department of Medical Oncology, Centre Hospitalier Universitaire Nantes, Nantes University, Nantes, France., Breysacher G; Gastroenterology Department, CH Pasteur, Colmar, France., Lagasse JP; Department of Gastroenterology, Hepatology and digestive Oncology, Centre Hospitalo-universitaire d'Orleans, Orleans, France., Lepage C; Burgundy Digestive Cancer Registry, INSERM U866, 21079, Dijon Cedex, France. Electronic address: come.lepage@u-bourgogne.fr., Valéry M; Medical Oncology Department, Gustave Roussy, F-94805, Villejuif, France., Bachet JB; Sorbonne University, Hepato-gastroenterology and digestive oncology department, Pitié Salpêtrière hospital, APHP, Paris, France. Electronic address: jean-baptiste.bachet@aphp.fr.
Jazyk: angličtina
Zdroj: Clinics and research in hepatology and gastroenterology [Clin Res Hepatol Gastroenterol] 2024 Dec 12, pp. 102514. Date of Electronic Publication: 2024 Dec 12.
DOI: 10.1016/j.clinre.2024.102514
Abstrakt: Aim of the Study: The management of synchronous metastatic rectal cancer (SMRC) is complex and multimodal, involving chemotherapy, surgery and/or radiotherapy. The aim of this study was firstly to confirm the efficacy of the induction FOLFIRINOX, and secondly to evaluate the different therapeutic strategies and outcomes of patients.
Patients and Methods: This French study combined data from a prospective FFCD trial and a multicenter cohort. Patients included had SMRC and had undergone induction triplet chemotherapy. Two groups of patients were defined according to the resectability of metastases at baseline: resectable (Res) and unresectable (URes). The primary endpoint was the objective response rate.
Results: 146 patients were included in 16 French centers and 65 patients in the FFCD1102 trial. In overall population the median age of patients was 59 years, 86% of tumors were of the lower or middle rectum, 33% were well-differentiated, 53% were RAS mutated and 7% BRAF mutated. Triplet induction was associated with 80% of objective response and 92% of disease control. After the induction phase, 69% and 48% of patients of Res and URes groups underwent rectal surgery, and secondary metastases resection was done in 79% and 39% of patients, respectively. Median overall survival (OS) for Res was 56.3 months (95% CI: 22.54-NA). Median OS for URes who had or not secondary metastases resection were 45.1 months (95% CI: 39.89-NA) and 21.1 months (95% CI 17.31-27.1), respectively. Patients with BRAF mutated tumors were more likely to have unresectable disease, and had worse survivals than the patients with RAS mutated or RAS/BRAF wild-type.
Conclusion: Triplet induction chemotherapy is a treatment of choice in selected patients with SMRC, allowing to adapt the therapeutic strategy to the response and invasiveness of the various sites.
Structured Abstract: The management of metastatic rectal cancer is essentially based on three main therapeutic approaches: surgery, radiotherapy/chemoradiotherapy and chemotherapy. Induction triplet chemotherapy appears as a good choice for fit and young patients. It allows to adapt the therapeutic strategy to the response and invasiveness of the various sites. In this study dedicated to patients undergoing treatment for rectal cancer with synchronous metastases, FOLFIRINOX-based induction chemotherapy was associated with objective response rate of 77% and disease control rate of 92%. These results are similar with those of the FFCD 1102 trial and confirm the efficacy of induction chemotherapy with FOLFIRINOX with or without targeted therapy in these patients in daily routine practice. Surgery for metastases is a key factor in determining patient's outcome and triplet induction chemotherapy, associated with high response rates, enables a significant percentage of patients to undergo surgery and appears therefore to be a treatment of choice, particularly for patients whose disease is unresectable at baseline.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jean Baptiste Bachet reports a relationship with Amgen Inc that includes: funding grants. Thierry Lecomte reports a relationship with Institut Servier SAS that includes: speaking and lecture fees. Anthony Turpin reports a relationship with Institut Servier SAS that includes: funding grants. David Tougeron reports a relationship with Sanofi that includes: speaking and lecture fees. Come Lepage reports a relationship with Takeda Oncology that includes: funding grants. *J.B. Bachet has received personal fees from Amgen, Bayer, Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme, Pierre Fabre, Sanofi, Servier, and non-financial support from Amgen, Merck Serono, and Roche, outside the submitted work. *T.Lecomte has received honoraria for speaking or consulting role from Servier, Pierre Fabre, Merck Serono, BMS, Astra Zeneca, AAA, Sanofi, IPSEN, Novartis, CHUGAI outside of the submitted work; research funding from Pierre Fabre and Leo Pharma outside of the submitted work; and travel grants from IPSEN, Merck Serono, AMGEN, Astra Zeneca, Pierre Fabre and Servier outside of the submitted work. *A.Turpin has received personal fees from Servier, Viatris, Incyte Bioscience, BMS, Merck and grants and personal fees from AstraZeneca and MSD outside the submitted work. *D.Tougeron has received honoraria as a speaker or in an advisory role from Sanofi, Roche, Merck Serono, Amgen, Servier, Pierre Fabre, BMS, Astra Zeneca, Takeda and MSD. *C.Lepage has received personal fees from Takeda, Pierre Fabre, Amgen, Servier, Novartis. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier Masson SAS.)
Databáze: MEDLINE
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