Biomarker-Guided Anti-Egfr Rechallenge Therapy in Metastatic Colorectal Cancer
Davide Ciardiello1,2, Giulia Martini1, Vincenzo Famiglietti1
1Oncologia Medica, Dipartimento di Medicina di Precisione, Università degli Studi della Campania Luigi Vanvitelli, 80131 Naples, Italy.
Abstract:
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.
Insights
Retreatment with anti-epidermal growth factor receptor (EGFR) antibodies may prolong survival in metastatic colorectal cancer (mCRC) patients. This strategy, known as rechallenge, shows promise, especially when guided by biomarkers like RAS and BRAF wild type status.
Area of Science:
- Oncology
- Medical Therapeutics
- Molecular Diagnostics
Background:
- Metastatic colorectal cancer (mCRC) patients progressing after first and second-line treatments have a poor prognosis.
- Emerging evidence suggests retreatment with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MAbs) can prolong survival in mCRC patients.
- This strategy, termed 'rechallenge,' is considered for patients who previously benefited from first-line anti-EGFR MAb plus chemotherapy.
Purpose of the Study:
- To review current knowledge on the anti-EGFR MAb rechallenge strategy in mCRC.
- To investigate the role of novel biomarkers in selecting patients for rechallenge therapy.
- To discuss ongoing clinical trials and future perspectives for anti-EGFR MAb rechallenge.
Main Methods:
- Review of existing literature on anti-EGFR MAb rechallenge in mCRC.
- Analysis of clinical data and biomarker studies, including liquid biopsy for RAS and BRAF status.
- Discussion of ongoing clinical trials and future research directions.
Main Results:
- Anti-EGFR MAb rechallenge has shown promising clinical activity in mCRC patients.
- Effectiveness is particularly noted in patients with plasma RAS and BRAF wild type circulating tumor DNA.
- A treatment break from anti-EGFR drugs may restore cancer cell sensitivity.
Conclusions:
- Anti-EGFR MAb rechallenge represents a potential therapeutic strategy to prolong survival in selected mCRC patients.
- Biomarker analysis, such as liquid biopsy for RAS and BRAF wild type status, is crucial for patient selection.
- Further research and ongoing trials are needed to optimize this approach.
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