期刊
ONCOLOGIST
卷 26, 期 8, 页码 668-675出版社
OXFORD UNIV PRESS
DOI: 10.1002/onco.13741
关键词
Colorectal cancer; Mismatch repair‐ deficient; Microsatellite instability high; Immune checkpoint inhibitors; BRAF; MLH1; PMS2; MSH2; MSH6; Liver metastasis
类别
资金
- Biostatistics Shared Resource of Winship Cancer Institute of Emory University
- National Institutes of Health/National Cancer Institutes [P30CA138292]
Liver metastasis, MLH1/PMS2 loss, BRAF V600E mutation, and age over 65 may predict the duration of response to immune checkpoint inhibitors in patients with MMR-D CRC.
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.
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