Prospective National Cohort Evaluating Predictive Biomarkers of Resistance to Immunotherapy in Patients With MSI/dMMR Metastatic Colorectal Cancer (CORESIM)

Summary

The Keynote 117 phase III trial demonstrated the superiority of pembrolizumab (anti-PD1 monoclonal antibody) versus chemotherapy +/- targeted therapy in first-line treatment of dMMR/MSI metastatic colorectal cancer (mCRC). However, primary resistance to pembrolizumab was observed in approximately 20-30% of patients treated in the Keynote 177 study. Therefore, the identification of biomarkers predictive of resistance to immunotherapy for dMMR/MSI mCRC is necessary to better select patients who benefit the most from immunotherapy, and those for whom other therapeutic approaches should be favored.

Eligibility

Inclusion Criteria:

* Patients over 18 years old
* Histologically confirmed colorectal adenocarcinoma with unresectable metastasis(s) receiving immunotherapy as first-line treatment with pembrolizumab
* Tumor with microsatellite instability determined by immunohistochemistry (loss of expression of MLH1, MSH2, MSH6 and/or PMS2) and/or by molecular biology (MSI-H on microsatellite analysis from tumor DNA according to practice routine of the center)

Exclusion Criteria:

* Patients with another concomitant cancer at the time of diagnosis requiring systemic treatment or impacting prognosis according to the medical team.
* Previous treatment with anti-PD1 or anti-PDL1.
* Previous treatment with chemotherapy +/- targeted therapy for MSI/dMMR metastatic colorectal cancer.
* Contraindication due to psychological or social reasons that may hinder follow-up (cognitive deficit, psychological disorders incompatible with obtaining non-opposition or consent; inability to be followed in the same center throughout the follow-up period for geographical reasons).
* Pregnant women
* persons under court protection or under protective supervision (guardianship or curatorship)
* Opposition to participation in the study.

Conditions3

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