Outcome of chemotherapy with or without targeted agents in metastatic colorectal cancer patients with deficient DNA mismatch repair: A single center, cohort study

AIMS: Metastatic colorectal cancer (mCRC) with deficient DNA mismatch repair (dMMR) is a rare disease accounting only for 4-5% of the whole mCRC and its optimal treatment still remains unclear. We conducted a retrospective study to evaluate the outcome of chemotherapy with or without bevacizumab or cetuximab in this setting. METHODS: A total of 729 colorectal cancer patients with dMMR status were screened for eligibility. The Kaplan-Meier method, the log-rank test and Cox analysis were utilized for survival analyses. RESULTS: A total of 43 patients met the inclusion criteria and enrolled in the study. The median overall survival (OS) of entire cohort was 21.7 months. Chemotherapy plus bevacizumab group exhibited a tendency of substantially higher overall response rate (ORR) than chemotherapy alone group (63.6% vs. 23.8%, P = 0.053), whereas the ORR between chemotherapy plus cetuximab group and chemotherapy alone group were similar (28.6% vs. 23.8%, P = 1.000). Compared with chemotherapy alone group, bevacizumab combined group achieved a significantly longer progression-free survival (10.0 months vs. 4.8 months, P = 0.028), whereas cetuximab combined group was not (6.8 months vs. 4.8 months, P = 0.158). Although the median OS seemed to favor bevacizumab combined group, no significant differences were detected between the three arms (33.7, 21.7 and 15.3 months, respectively; P = 0.345). Prognostic analysis showed that primary tumor resection was the positive prognostic factor of OS (hazards ratio: 0.438; P = 0.041). CONCLUSION: dMMR mCRC seems resistant to chemotherapy and cetuximab. Bevacizumab combined therapy shows a sign of potentially favorable outcome in this subtype.