Biomarker-guided anti-egfr rechallenge therapy in metastatic colorectal cancer

Davide Ciardiello, Giulia Martini, Vincenzo Famiglietti, Stefania Napolitano, Vincenzo De Falco, Teresa Troiani, Tiziana Pia Latiano, Javier Ros, Elena Elez Fernandez, Pietro Paolo Vitiello, Evaristo Maiello, Fortunato Ciardiello, Erika Martinelli

Research output: Contribution to journalReview articlepeer-review


The prognosis of patients with metastatic colorectal cancer (mCRC) who progressed to the first and the second lines of treatment is poor. Thus, new therapeutic strategies are needed. During the last years, emerging evidence suggests that retreatment with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MAbs) in the third line of mCRC patients, that have previously obtained clinical benefit by first-line therapy with anti-EGFR MAbs plus chemotherapy, could lead to prolonged survival. The rationale beyond this “rechallenge” strategy is that, after disease progression to first line EGFR-based therapy, a treatment break from anti-EGFR drugs results in RAS mutant cancer cell decay, restoring the sensitivity of cancer cells to cetuximab and panitumumab. In fact, rechallenge treatment with anti-EGFR drugs has shown promising clinical activity, particularly in patients with plasma RAS and BRAF wild type circulating tumor DNA, as defined by liquid biopsy analysis at baseline treatment. The aim of this review is to analyze the current knowledge on rechallenge and to investigate the role of novel biomarkers that can guide the appropriate selection of patients that could benefit from this therapeutic strategy. Finally, we discuss on-going trials and future perspectives.

Original languageEnglish
Article number1941
Issue number8
Publication statusPublished - Apr 2 2021


  • Anti-EGFR monoclonal antibodies
  • Metastatic colorectal cancer
  • Rechallenge

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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