Association of Primary Resistance to Immune Checkpoint Inhibitors in Metastatic Colorectal Cancer With Misdiagnosis of Microsatellite Instability or Mismatch Repair Deficiency Status

作者：Romain Cohen, Élisabeth Hain, Olivier Buhard, Agathe Guilloux, Armelle Bardier, Rachid Kaci, Philippe Bertheau, Florence Renaud, Frédéric Bibeau, Jean–François Fléjou, Thierry André, Magali Svrcek, Alex Duval · 发表于：JAMA Oncology · 年份：2018 · DOI：10.1001/jamaoncol.2018.4942 · 被引用次数：251 · 研究领域：Genetic factors in colorectal cancer、Cancer Immunotherapy and Biomarkers、Colorectal Cancer Treatments and Studies

IMPORTANCE: Primary resistance to immune checkpoint inhibitors is observed in 10% to 40% of patients with metastatic colorectal cancer (mCRC) displaying microsatellite instability (MSI) or defective mismatch repair (dMMR). OBJECTIVE: To investigate possible mechanisms underlying primary resistance to immune checkpoint inhibitors of mCRC displaying MSI or dMMR. DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis of a single-center, prospective cohort included 38 patients with mCRC diagnosed as MSI or dMMR by local laboratories and entered into trials of immune checkpoint inhibitors between January 1, 2015, and December 31, 2016. The accuracy of MSI or dMMR status was also assessed in a retrospective cohort comprising 93 cases of mCRC that were diagnosed as MSI or dMMR between January 1, 1998, and December 31, 2016, in 6 French hospitals. Primary resistance of mCRC was defined as progressive disease according to Response Evaluation Criteria in Solid Tumors criteria, 6 to 8 weeks after initiation of immune checkpoint inhibitors, without pseudo-progression. All tumor samples were reassessed for dMMR status using immunohistochemistry with antibodies directed against MLH1, MSH2, MSH6, and PMS2, and for MSI using polymerase chain reaction with pentaplex markers and with the HSP110 T17 (HT17) repeat. MAIN OUTCOMES AND MEASURES: The primary outcome was positive predictive value. RESULTS: Among the 38 patients (15 women and 23 men; mean [SD] age, 55.6 [13.7] years) in the study w...