Rechallenge with anti-EGFR antibodies in metastatic colorectal cancer: A single center analysis

Colorectal cancer remains the third most common cancer, and its management has been dramatically affected by the advent of molecular profiling. Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies are today a fundamental piece in the first or second-line treatment of RAS-wild-type metastatic colorectal cancer. In subsequent lines, patients whose disease initially responded to anti-EGFR antibodies may experience benefit with the re-administration of this agent. Even though the analysis of circulating tumor DNA seems the most appropriate instrument for identifying the best candidates for retreatment, the assessment of molecular alterations on ctDNA is not routinely practiced worldwide. Some clinical surrogates of sensitivity to anti-EGFRs have been described as predictors of efficacy in the rechallenge setting. Bearing this in mind, we explored the association of several potential clinical predictors of benefit to treatment outcomes in our institution in patients retreated in later lines with anti-EGFRs.

Patients with metastatic colorectal cancer who had been retreated with anti-EGFRs between 2015 and 2021 were identified. Clinical characteristics were retrospectively assessed, as were oncological outcomes. Kaplan Meyer analysis was used to assess progression-free survival (PFS) and overall survival (OS), and the association of variables potentially related to anti-EGFR sensitivity was investigated.

A total of 14 patients were identified, of which 4 were females (28.5%) and 10 were males (71.5%). The median age at diagnosis was 59 years old (45-70). Only two patients had been assessed for ctDNA, with both maintaining RAS-wild type. A longer anti-EGFR-free interval and rechallenging in the third line (vs fourth line setting) were associated with longer PFS but not OS. No statistically significant association of clinical characteristics with oncological outcomes (OS and PFS) were identified. The median interval time between initial anti-EGFR and retreatment was 14.3 months. Median PFS and OS from the date of rechallenge were 6.1 and 9.8 months, respectively.

Retreatment with anti-EGFR provides disease control and clinical benefit. Clinical characteristics were not trustworthy predictors of response to anti-EGFR rechallenge.

The authors.

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All authors have declared no conflicts of interest.