Occurence of RAS reversion in metastatic colorectal cancer patients treated with bevacizumab
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Samantha Epistolio1,*, Marco Cefalì2,*, Paolo Spina1,3, Francesca Molinari1, Alessandra Movilia4, Massimiliano Cergnul5, Luca Mazzucchelli1, Sara De Dosso2, Milo Frattini1,# and Piercarlo Saletti2,6,#
1 Institute of Pathology, EOC, Locarno, Switzerland
2 Oncology Institute of Southern Switzerland, EOC, Bellinzona, Switzerland
3 Department of Health Sciences, University of Eastern Piedmont, Novara, Italy
4 Department of Pathology, ASST Ovest Milanese, Ospedale di Legnano, Legnano, Italy
5 Department of Medical Oncology, ASST Ovest Milanese, Ospedale di Legnano, Legnano, Italy
6 Current address: Department of Medical Oncology, Clinica Luganese Moncucco, Lugano, Switzerland
* These authors are Joined First Authors
# These authors are Joint Senior Authors
Keywords: RAS mutations; bevacizumab; metastatic colorectal cancer; next-generation sequencing
Received: March 23, 2021 Accepted: May 03, 2021 Published: May 25, 2021
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.
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