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.