A multicenter study evaluating efficacy of immune checkpoint inhibitors in advanced non-colorectal digestive cancers with microsatellite instability
- PMID: 38537314
- DOI: 10.1016/j.ejca.2024.114033
A multicenter study evaluating efficacy of immune checkpoint inhibitors in advanced non-colorectal digestive cancers with microsatellite instability
Abstract
Background: One randomized phase III trial comparing chemotherapy (CT) with immune checkpoint inhibitors (ICI) has demonstrated significant efficacy of ICI in deficient DNA mismatch repair system/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer. However, few studies have compared ICI with CT in other advanced dMMR/MSI-H digestive tumors.
Methods: In this multicenter study, we included patients with advanced dMMR/MSI-H non-colorectal digestive tumors treated with chemotherapy and/or ICIs. Patients were divided retrospectively into two groups, a CT group and an immunotherapy (IO) group. The primary endpoint was progression-free survival (PFS). A propensity score approach using the inverse probability of treatment weighting (IPTW) method was applied to deal with potential differences between the two groups.
Results: 133 patients (45.1/27.1/27.8% with gastric/small bowel/other carcinomas) were included. The majority of patients received ICI in 1st (29.1%) or 2nd line (44.4%). The 24-month PFS rates were 7.9% in the CT group and 71.2% in the IO group. Using the IPTW method, IO treatment was associated with better PFS (HR=0.227; 95% CI 0.147-0.351; p < 0.0001). The overall response rate was 26.3% in the CT group versus 60.7% in the IO group (p < 0.001) with prolonged duration of disease control in the IO group (p < 0.001). In multivariable analysis, predictive factors of PFS for patients treated with IO were good performance status, absence of liver metastasis and prior primary tumor resection, whereas no association was found for the site of the primary tumor.
Conclusions: In the absence of randomized trials, our study highlights the superior efficacy of ICI compared with standard-of-care therapy in patients with unresectable or metastatic dMMR/MSI-H non-colorectal digestive cancer, regardless of tumor type, with acceptable toxicity.
Keywords: Chemotherapy; Deficient mismatch repair; Digestive cancers; Immune checkpoint inhibitors; Microsatellite instability.
Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.
Conflict of interest statement
Declaration of Competing Interest AH reports advisory/consultancy fees from Amgen, AstraZeneca, Debiopharm, Eli Lilly and Company, Incyte Corporation, QED Therapeutics. AT has received personal fees from MSD, BMS, Merck Serono, Pierre Fabre, Servier, Incyte Biosciences, Viatris, AstraZeneca. CG has participated in consulting and/or advisory fees for Servier, Sanofi, Merck, has received honoraria as invited speaker from Pierre Fabre, and has received support for travel to meetings from Amgen. DT reports consultancy, advisory fees, honoraria from Servier, Pierre Fabre, Merck Serono, MSD, BMS, AZ, Roche, Sanofi; research funding from Sandoz, AstraZenenca, Servier, MSD; travel grants from Pierre Fabre, MSD, Servier, Roche. EAl reports consultancy and honoraria from Servier, AMGEN, MSD and Merck Serono. EAu reports honoraria from Amgen and Sanofi. FS reports consultancy, advisory fees, honoraria from AMAL Therapeutics, Bayer, BMS, Dragonfly Therapeutics, Merck, Nordic Pharma, Roche, Servier; research funding (institutional) from Amgen, Astra Zeneca, Bayer, BMS, Roche, Sanofi, Travel grants from Amgen, Bayer, Lilly, Servier; and leadership roles at Co-Chair EORTC Task Force Colon, Rectum, Anal Canal. JT has received honoraria as a speaker or in an advisory role from Sanofi, Roche, Merck Serono, Amgen, Servier, Pierre Fabre, Lilly, AstraZeneca and MSD. MBA has received honoraria as a speaker or in an advisory role from BMS, AMGEN, INCYTE, Servier, Pierre Fabre, MercK Serono, Deciphera, Mundipharma, Bayer. RC has received personal fees from Bristol-Myers Squibb, Exeliom Biosciences, Enterome Bioscience, MSD Oncology, Mylan Medical, Pierre Fabre, Servier and non-financial support. RG reports advisory fees from Amgen, AstraZeneca, MSD, Pierre Fabre and travel expenses from BMS. SK reports consultancy, advisory roles, honoraria from Amgen, BeiGene, Boehringer-Ingelheim, Merck, MSD, Pfizer, Servier, and research funding from Behringer-Ingelheim, Bristol-Myers Squibb, Novartis, Roche. SP reports honoraria as a speaker or in an advisory role from Amgen, Pierre Fabre, Servier, BMS, MSD, Merck Serono, Bayer, Sanofi. TAn reports attending advisory board meetings and receiving consulting fees from Astellas, Aptitude Health, Bristol Myers Squibb, Gritstone Oncology, GamaMabs Pharma Sa, Gilead, GlaxoSmithKline, Merck & Co. Inc., Nordic Oncology, Pierre Fabre, Seagen, Servier and Transgène; honoraria from Bristol Myers Squibb, GlaxoSmithKline, Merck & Co. Inc., Merck Serono, Pierre Fabre, Roche Sanofi, Seagen and Servier and support for meetings from Merck & Co. Inc. and Servier. TAp reports honoraria from Amgen, Pierre Fabre, Servier and advisory fees from BMS, MSD, Pierre Fabre. TM reports consultancy, advisory fees, honoraria from Servier, Pierre Fabre, Merck Serono, AAA, Sanofi, and research funding from Amgen; travel grants from Pierre Fabre, Merck Serono, Sanofi. VH reports consultancy, advisory roles, honoraria from AAA, Amgen, Esteve, Ipsen, Deciphera, Servier, Pierre Fabre, Merck Serono. All other authors have declared no conflicts of interest.
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