Retreatment With Anti-EGFR Antibodies in Metastatic Colorectal Cancer Patients: A Multi-institutional Analysis

Liquid biopsy is a promising tool to predict benefit from antieepidermal growth factor receptor (EGFR) retreatment in metastatic colorectal cancer patients. However, this technique is far from ready for routine clinical practice. Therefore, we identified 86 patients in a real-life database of 5530 patients to explore clinical features expected to predict benefit from anti-EGFR retreatment; however, none of these factors was predictive of response to anti-EGFR retreatment. Background: On the basis of retrospective analyses and phase 2 studies, metastatic colorectal cancer patients whose disease responded to a first-line regimen containing an antieepidermal growth factor receptor (EGFR) agent may experience benefit from anti-EGFR readministration in later therapy lines. While the analysis of circulating tumor DNA seems a promising tool to select the best candidates for this strategy, identifying clinical predictors of anti-EGFR sensitivity would be useful to drive treatment choices in daily practice. Patients and Methods: A real-life database of 5530 patients treated at 6 institutions was queried. Included were patients who were retreated with anti-EGFRs, who had RAS/BRAF wild-typeestatus tissue samples, who had received a first-line anti-EGFRebased regimen with at least stable disease as best response, and who had received at least one further line of therapy before anti-EGFR retreatment. 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: A total of 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 first-line progressive disease of < 3 months (rechallenge group), > 2 prior therapy lines and a longer anti-EGFRefree interval were associated with higher ORR, but not with longer PFS or OS. Conclusion: Clinical features we deemed surrogates of anti-EGFR sensitivity were not reliable predictors of benefit from anti-EGFR retreatment. (C) 2020 Elsevier Inc. All rights reserved.