Re-treatment with anti-EGFR Antibodies in Metastatic Colorectal Cancer Patients: a multi-institutional analysis.

Abstract Background Based on retrospective analyses and phase II studies, metastatic colorectal cancer (mCRC) patients who responded to a 1st-line regimen containing an anti-epidermal growth factor receptor (EGFR) agent may achieve benefit from the anti-EGFR re-administration in later lines. While the analysis of circulating tumor DNA (ctDNA) seems a promising tool to select the best candidates to this strategy, identifying clinical predictors of anti-EGFR sensitivity would be useful to drive treatment choices in the daily practice. Patients and Methods A real-life database of 5530 patients treated at 6 institutions was queried. Patients retreated with anti-EGFRs, with RAS/BRAF wild-type status on tissue samples, who had received a 1st-line anti-EGFR-based regimen with at least SD as best response, and at least one further line of therapy before anti-EGFR re-treatment, were included. The association with Overall Response Rate (ORR), Progression Free Survival (PFS) and Overall Survival (OS) of variables potentially related to anti-EGFR sensitivity was investigated. Results 86 patients were identified. The ORR during anti-EGFR retreatment was 19.8%, median PFS and OS were 3.8 and 10.2 months, respectively. No significant association of clinical features of anti-EGFR sensitivity with ORR, PFS and OS was observed. Among the 56 patients with a time from the last anti-EGFR administration to 1st-line PD (Progressive Disease) shorter than 3 months (rechallenge group), more than 2 prior lines and a longer anti-EGFR free interval were associated with higher ORR, but not with longer PFS or OS. Conclusions Clinical features deemed as surrogates of anti-EGFR sensitivity are not reliable predictors of benefit from anti-EGFR re-treatment.