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

IF 2.6 4区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Clinics and research in hepatology and gastroenterology Pub Date : 2025-01-01 DOI:10.1016/j.clinre.2024.102514

Victoire Dabout , Laurent Mineur , David Tougeron , Karine Le Malicot , Claire Gallois , Jean Marc Phelip , Anthony Turpin , Romain Cohen , Benedicte Demoustier , Vincent Hautefeuille , Christophe Locher , Charles-Briac Levaché , Emmanuel Mitry , Thierry Lecomte , Fabien Brocard , Deborah Hassid , Marie Porte , Gilles Breysacher , Jean-Paul Lagasse , Côme Lepage , Jean-Baptiste Bachet

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引用次数: 0

Abstract

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.

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直肠腺癌和同步转移患者的诱导三联化疗，AGEO-FFCD 研究。

研究目的：同步转移性直肠癌（SMRC）的治疗是复杂和多模式的，包括化疗、手术和/或放疗。本研究的目的首先是确认诱导FOLFIRINOX的疗效，其次是评估不同的治疗策略和患者的结果。患者和方法：这项法国研究结合了前瞻性FFCD试验和多中心队列研究的数据。纳入的患者患有SMRC并接受了诱导三联化疗。根据基线转移的可切除性定义两组患者：可切除（Res）和不可切除（URes）。主要终点为客观有效率。结果：146名患者被纳入16个法国中心，65名患者被纳入FFCD1102试验。在总体人群中，患者的中位年龄为59岁，86%的肿瘤位于直肠下部或中部，33%的肿瘤分化良好，53%的肿瘤发生RAS突变，7%的肿瘤发生BRAF突变。三胞胎诱导与80%的客观反应和92%的疾病控制相关。诱导期结束后，Res组和URes组分别有69%和48%的患者进行了直肠手术，分别有79%和39%的患者进行了继发转移切除。Res的中位总生存期（OS）为56.3个月（95% CI: 22.54-NA）。有或没有继发转移切除的ure的中位生存期分别为45.1个月（95% CI: 39.89-NA）和21.1个月（95% CI: 17.31-27.1）。与RAS突变或RAS/BRAF野生型患者相比，BRAF突变肿瘤患者更容易发生不可切除的疾病，生存率更差。结论：三联体诱导化疗是SMRC患者的一种治疗选择，可以根据不同部位的反应和侵袭性调整治疗策略。摘要：转移性直肠癌的治疗基本上基于三种主要的治疗方法：手术、放疗/放化疗和化疗。诱导三联化疗似乎是健康和年轻患者的良好选择。它可以使治疗策略适应不同部位的反应和侵袭性。在这项针对直肠癌同步转移患者的研究中，基于folfirinox的诱导化疗的客观缓解率为77%，疾病控制率为92%。这些结果与FFCD 1102试验的结果相似，在日常实践中证实了FOLFIRINOX诱导化疗联合或不联合靶向治疗对这些患者的疗效。手术治疗转移是决定患者预后的关键因素，三联体诱导化疗具有高反应率，使很大比例的患者能够接受手术治疗，因此似乎是一种治疗选择，特别是对于基线时无法切除的患者。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinics and research in hepatology and gastroenterology GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

4.30

自引率

3.70%

发文量

198

审稿时长

42 days

期刊介绍： Clinics and Research in Hepatology and Gastroenterology publishes high-quality original research papers in the field of hepatology and gastroenterology. The editors put the accent on rapid communication of new research and clinical developments and so called "hot topic" issues. Following a clear Editorial line, besides original articles and case reports, each issue features editorials, commentaries and reviews. The journal encourages research and discussion between all those involved in the specialty on an international level. All articles are peer reviewed by international experts, the articles in press are online and indexed in the international databases (Current Contents, Pubmed, Scopus, Science Direct). Clinics and Research in Hepatology and Gastroenterology is a subscription journal (with optional open access), which allows you to publish your research without any cost to you (unless you proactively chose the open access option). Your article will be available to all researchers around the globe whose institution has a subscription to the journal.