Efficacy of Anti-EGFR in Microsatellite Instability Metastatic Colorectal Cancer Depending on Sporadic or Familial Origin

Abstract

Anti-epidermal growth factor receptor (EGFR) efficacy in patients with microsatellite instability (MSI) metastatic colorectal cancer (mCRC) according to sporadic vs familial origin is unknown. We retrospectively analyzed 128 patients with MSI mCRC treated with first-line chemotherapy ± anti-EGFR. Among them, 61 and 67 patients were respectively categorized as familial and sporadic based on mismatch repair protein immunostaining, BRAF mutational status, and MLH1 promoter methylation status. We observed that addition of anti-EGFR to chemotherapy was associated with a statistically significant improvement of progression-free survival for familial (median = 5.0 vs 10.2 months, hazard ratio [HR] = 0.47, 95% confidence interval [CI] = 0.23 to 0.94; P = .03) but not for sporadic (median = 4.4 vs 5.4 months, HR = 0.80, 95% CI = 0.39 to 1.60; P = .52) MSI mCRC patients. In multivariate analysis, the survival benefit of adding anti-EGFR to chemotherapy remained statistically significant for familial MSI cases (P = .04). These findings deserve to be confirmed in a prospective study and could help decision making in MSI mCRC without access or resistant to immunotherapy.

Figure 1.

Progression-free survival in patients with sporadic or familial MSI metastatic colorectal cancer treated with first-line by chemotherapy alone or combined with anti-EGFR monoclonal antibody. For sporadic MSI cases (A), multivariate analysis was adjusted on variables with P values of no more than .10 in univariate analyses (ie, number of metastatic sites and peritoneal metastases). The IPTW was applied in the Cox regression model using the propensity score based on tumor differentiation and chemotherapy regimen. For familial MSI cases (B), multivariate analysis was adjusted on variables with P values of no more than .10 in univariate analyses (ie, gender and surgery of primary tumor). The IPTW was applied in the Cox regression model using the propensity score based on synchronicity of metastases, lymph nodes metastases, and chemotherapy regimen. All statistical tests were 2-sided. Anti-EGFR = anti-epidermal growth factor receptor; chemo = chemotherapy; CI = confidence interval; HR = hazard ratio; IPTW = inverse probability of treatment weighting; MA = multivariate analysis; MSI = microsatellite instability; UA = univariate analysis.