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Ref Type Journal Article
PMID (38537314)
Authors Moreau M, Alouani E, Flecchia C, Falcoz A, Gallois C, Auclin E, André T, Cohen R, Hollebecque A, Turpin A, Pernot S, Masson T, Di Fiore F, Dutherge M, Mazard T, Hautefeuille V, Van Laethem JL, De la Fouchardière C, Perkins G, Ben-Abdelghani M, Sclafani F, Aparicio T, Kim S, Vernerey D, Taieb J, Guimbaud R, Tougeron D
Title A multicenter study evaluating efficacy of immune checkpoint inhibitors in advanced non-colorectal digestive cancers with microsatellite instability.
URL
Abstract Text 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.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.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.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.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
MLH1 negative gastrointestinal system cancer predicted - sensitive unspecified immune checkpoint inhibitor Clinical Study Actionable In a retrospective analysis, first-line treatment with immune checkpoint inhibitors (n=30) improved overall response rate (60.7% vs 26.3%; p=0.0005), 24-month progression-free survival (PFS) rate (71.2% vs 7.9%), and median PFS (5.5 months vs not reached; HR=0.21, p<0.0001) compared to first-line chemotherapy (n=103) in patients with mismatch repair-deficient (dMMR) and/or microsatellite instability-high (MSI-H) non-colorectal digestive tract cancers, including pancreatic cancer (PMID: 38537314). 38537314
MSH6 negative gastrointestinal system cancer predicted - sensitive unspecified immune checkpoint inhibitor Clinical Study Actionable In a retrospective analysis, first-line treatment with immune checkpoint inhibitors (n=30) improved overall response rate (60.7% vs 26.3%; p=0.0005), 24-month progression-free survival (PFS) rate (71.2% vs 7.9%), and median PFS (5.5 months vs not reached; HR=0.21, p<0.0001) compared to first-line chemotherapy (n=103) in patients with mismatch repair-deficient (dMMR) and/or microsatellite instability-high (MSI-H) non-colorectal digestive tract cancers, including pancreatic cancer (PMID: 38537314). 38537314