Abstract
Background: A disappearance of RAS mutations in the plasma of about 50% of mCRCs (metastatic colorectal cancers) treated with bevacizumab-based chemotherapy has been reported. Our aim was to evaluate the same issue at tissue level.Materials and Methods: Using next-generation sequencing and real-time PCR approaches, we characterized the primary tumor (PT) and paired liver metastases in 28 RAS mutant mCRCs. Patients were subdivided into 3 treatment groups: 1) bevacizumab plus chemotherapy; 2) chemotherapy alone; 3) any systemic therapy (control group). In groups 1 and 2, liver metastases were resected after removal of PT and subsequent neoadjuvant systemic therapy.Results: RAS mutant alleles are at the same percentage in PT and liver metastases in the control group, while a significant reduction of the level of RAS mutations was detected in 57.1% of cases in group 1 and in 8.3% of cases in group 2. Differences among groups are statistically significant (p = 0.038).Conclusions: Most of mCRC patients treated with bevacizumab-containing regimens experience a strong reduction of RAS mutant cells, suggesting bevacizumab as particularly active against RAS mutant cells. This finding might have potential therapeutic implications, as anti-EGFR could be reconsidered in primarily RAS mutant patients reverted to a wild-type status after bevacizumab exposure.
Highlights
The overall survival (OS) for patients with metastatic colorectal cancer has markedly improved within the last 2 decades, reaching approximately 30 months [1,2,3].The therapeutic options include fluoropyrimidines, oxaliplatin and irinotecan combinations with one anti-vascular endothelial growth factor compound, and/or anti-epidermal growth factor receptor (EGFR) monoclonal antibody (MoAb, namely cetuximab or panitumumab) for patients with RAS/ BRAF wild-type status, administered across different treatment lines [4]
RAS mutant alleles are at the same percentage in primary tumor (PT) and liver metastases in the control group, while a significant reduction of the level of RAS mutations was detected in 57.1% of cases in group 1 and in 8.3% of cases in group 2
Most of metastatic colorectal cancer (mCRC) patients treated with bevacizumab-containing regimens experience a strong reduction of RAS mutant cells, suggesting bevacizumab as active against RAS mutant cells
Summary
The therapeutic options include fluoropyrimidines, oxaliplatin and irinotecan combinations (either doublets or triplets) with one anti-vascular endothelial growth factor (anti-VEGF) compound (i.e., bevacizumab, aflibercept and ramucirumab), and/or anti-epidermal growth factor receptor (EGFR) monoclonal antibody (MoAb, namely cetuximab or panitumumab) for patients with RAS/ BRAF wild-type status, administered across different treatment lines [4]. In first-line, data support the use of anti-EGFR MoAbs in patients with left-sided, RAS and BRAF wild-type tumors, whilst bevacizumab is preferred in combination with chemo-doublets or -triplet in RAS/BRAF mutated tumors or RAS/BRAF wild-type right-sided primaries [10, 11]. A disappearance of RAS mutations in the plasma of about 50% of mCRCs (metastatic colorectal cancers) treated with bevacizumab-based chemotherapy has been reported. Our aim was to evaluate the same issue at tissue level
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