Efficacy of Anti-VEGF and Anti-EGFRs in Microsatellite Instable (MSI-H) Metastatic Colorectal Cancer in a Turkish Oncology Group (TOG) Cohort Study

Abstract

Background: Mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal tumors constitute 5% of metastatic colorectal cancer(mCRC). Immunotherapy is a new standard, but it is difficult to provide for all patients. 5-Flurouracil-based treatment with anti-EGFRs (cetuximab and panitumumab) in RAS/BRAF-wild or anti-VEGF (bevacizumab) is used in mCRC. Data is limited for the efficacy of anti-VEGF or anti-EGFRs in dMMR/MSI-H mCRC due to the small number of cases in the colorectal cancer population in trials. Aims: To evaluate prognostic factors in dMMR/MSI-H mCRC and compare progression-free survival time of patients receiving anti-VEGF and anti-EGFR combined with first-line 5FU-based therapy. Methods: Patients with metastatic dMMR/MSI-H colorectal cancer diagnosed between January 2015 and January 2023 were included in this cohort study. Progression-free survival times of patients treated with first-line therapy were compared. Prognostic factors associated with overall survival were investigated. Results: A total of 132 patients were included. Mutation rates were 35.6% (n:47) for RAS and 12.1% (n: 16) for BRAF (. Median progression-free survival (PFS) was 10.9 (95% CI: 9.2-12.6) months. Median overall survival (OS) was 44 months (95% CI: 26.23-63.03). 82 (62.1%) patients had primary tumor resection (PTR), 26 (19.7%) had PTR and metastasectomy. A total of 17 (12.8%) de novo mCRC patients had maximal cytoreductive surgery (MCS). A total of 14 (10.6%) patients had subsequent immunotherapy (IO). In multivariate analysis, RAS/BRAF mutation status, MCS, and subsequent IO are defined as prognostic factors for OS (p < 0.01, p: 0.022, and p: 0.005, respectively). No statistically significant difference (PFS, OS) was found in patients receiving first-line anti-VEGF or anti-EGFR therapy. Conclusions: dMMR/MSI-H mCRC is an entity with different tumor biology. We consider that dMMR/MSI-H mCRC patients with BRAF wild, MCS and subsequent IO have better outcomes with 1st line 5FU-based treatment with anti-VEGF/anti-EGFRs.