Mismatch Repair (MMR) Gene Alteration and BRAF V600E Mutation Are Potential Predictive Biomarkers of Immune Checkpoint Inhibitors in MMR-Deficient Colorectal Cancer. (22nd March 2021)

• Record Type: Journal Article
• Authors: Sahin, Ibrahim Halil; Goyal, Subir; Pumpalova, Yoanna; Sonbol, Mohamad B.; Das, Satya; Haraldsdottir, Sigurdis; Ahn, Daniel; Ciombor, Kristen K.; Chen, Zhengjia; Draper, Amber; Berlin, Jordan; Bekaii-Saab, Tanios; Lesinski, Gregory B.; El-Rayes, Bassel F.; Wu, Christina
• Is Part Of: Oncologist. Volume 26:Number 8(2021)
• Page Start: 668
• Page End: 675
• Publication Date: 2021-03-22
• Subjects: Colorectal cancer -- Mismatch repair-deficient -- Microsatellite instability high -- Immune checkpoint inhibitors -- BRAF -- MLH1 -- PMS2 -- MSH2 -- MSH6 -- Liver metastasis; Oncology -- Periodicals; Tumors -- Periodicals; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Oncology; Tumors; Neoplasms; Electronic journals; Periodicals; Periodicals; 616.994
• DOI: 10.1002/onco.13741
• Languages: English
• ISSNs: 1083-7159

Abstract

Abstract : 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 < .001). There were improved 1-year and 2-year PFS rates in patients with wild-type BRAF when compared with patients with BRAF V600E mutation (73.3% vs. 40%, and 73.3% vs. 26.7%; respectively; p < .001). Patients aged >65 had significantly worse PFS rates as compared with patients aged ≤65 ( p < .001). Conclusion: BRAF V600E mutation, MLH1 and/or PMS2 loss, as well as age >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. Abstract : This article examines the effect of molecular subsets of mismatch repair-deficient (MMR-D) colorectal cancer and BRAF V600E mutation status as a molecular biomarker of immune checkpoint inhibitor efficacy in patients with MMR-D colorectal cancer.