Mismatch Repair (MMR) Gene Alteration and BRAF V600E Mutation Are Potential Predictive Biomarkers of Immune Checkpoint Inhibitors in MMR-Deficient Colorectal Cancer

The oncologist

article

Ibrahim Halil Sahin¹  Amber Draper²  Jordan Berlin³  Tanios Bekaii-Saab⁴  Gregory B. Lesinski²  Bassel F. El-Rayes²  Christina Wu²  Subir Goyal²  Yoanna Pumpalova⁵  Mohamad B. Sonbol⁴  Satya Das³  Sigurdis Haraldsdottir⁶  Daniel Ahn⁴  Kristen K. Ciombor³  Zhengjia Chen² 

[1] H. Lee Moffitt Cancer Center and Research Institute;Emory University School of Medicine, Winship Cancer Institute;Vanderbilt University Ingram Cancer Center;Mayo Clinic;Stanford University Cancer Institute;Dana-Farber Cancer Institute

关键词: Colorectal cancer;    Mismatch repair-deficient;    Microsatellite instability high;    Immune checkpoint inhibitors;    BRAF;    MLH1;    PMS2;    MSH2;    MSH6;    Liver metastasis;   

DOI  :  10.1002/onco.13741

学科分类：地质学

来源: AlphaMed Press Incorporated

【 摘 要 】

Background Immune checkpoint inhibitor (ICI) therapy is highly effective in metastatic mismatch repair-deficient (MMR-D) colorectal cancer (CRC). In this study, we evaluated molecular and clinical predictors of ICI response in MMR-D CRC. Materials and Methods Patient databases at four cancer institutions were queried. The Fisher exact test was performed to test the association of clinical and molecular markers. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and compared by the log-rank test. Twelve- and 24-month PFS rates were compared by the Z test. Results A total of 60 patients with CRC with MMR-D/microsatellite instability-high who previously received ICIs were identified. Patients with liver metastasis had a lower overall response rate as compared with other sites of metastasis (36.4% vs. 68.7%; p = .081). Patients with MLH1/PMS2 loss had worse 1-year and 2-year PFS rates compared with patients with MSH2/MSH6 loss (84.2% vs. 57.8% and 78.2% vs. 54.2%, respectively; p 65 had significantly worse PFS rates as compared with patients aged ≤65 ( p 65 years and liver metastasis, may be predictive of duration of ICI response in patients with MMR-D CRC. Larger cohorts are needed to confirm our findings. Implications for Practice The results of this study reveal clinically important biomarkers that potentially predict immune checkpoint inhibitor response in patients with mismatch repair-deficient colorectal cancer.

【 授权许可】

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