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

Asia Pac J Clin Oncol. 2019 Jun;15(3):128-135. doi: 10.1111/ajco.13130. Epub 2019 Jan 29.

Abstract

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.

Keywords: chemotherapy; deficient DNA mismatch repair; metastatic colorectal cancer; prognosis; targeted therapy.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab / administration & dosage*
  • Cetuximab / administration & dosage*
  • Cohort Studies
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • DNA Mismatch Repair / physiology
  • DNA Repair Enzymes / deficiency
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Bevacizumab
  • DNA Repair Enzymes
  • Cetuximab