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

## TL;DR

This study examines treatment outcomes in a specific type of colorectal cancer, finding that certain factors like BRAF mutations and surgery may influence survival, though anti-VEGF and anti-EGFR therapies showed no significant difference.

## Contribution

The study provides insights into prognostic factors and treatment efficacy in a rare subset of metastatic colorectal cancer patients with microsatellite instability.

## Key findings

- No statistically significant difference in progression-free survival between anti-VEGF and anti-EGFR therapies.
- BRAF mutation, maximal cytoreduction, and subsequent immunotherapy were associated with better prognosis.
- Median overall survival was 44 months in the studied cohort.

## Abstract

Colorectal cancer is a widespread health problem at present. Despite recent advances in metastatic colorectal cancer, median survival remains low. Microsatellite instability-high (MSI-H) colorectal cancer accounts for approximately 5% of all metastatic colorectal cancer patients and has a different tumor biology than other colorectal cancer patients. In our study, we evaluated the efficacy of commonly used targeted therapies in this subgroup of metastatic colorectal cancer patients. While we did not find a statistically significant difference between targeted therapies, we found that progression-free survival was numerically higher with bevacizumab. Furthermore, we found that BRAF mutation, maximal cytoreduction, and the use of second-line and subsequent immunotherapy were associated with prognosis.

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.