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Genotype-based selection of treatment of patients with advanced colorectal cancer (SETICC): a pharmacogenetic-based

A Abad1, E Martínez-Balibrea2, J M Viéitez3

  • 1Medical Oncology Service, Catalan Institute of Oncology, Badalona, Spain.

Annals of Oncology : Official Journal of the European Society for Medical Oncology
|November 18, 2017
PubMed
Abstract

Insights

Personalizing metastatic colorectal cancer therapy using TYMS and ERCC1 polymorphisms did not improve survival. However, tailored treatment showed higher response rates and fewer toxicities, warranting further study.

Area of Science:

  • Oncology
  • Pharmacogenomics
  • Clinical Trials

Background:

  • Personalized therapy for metastatic colorectal cancer (mCRC) remains challenging.
  • TYMS-3' untranslated region (UTR) and ERCC1-118C/T polymorphisms may guide fluoropyrimidine and oxaliplatin selection.
  • This study evaluated these polymorphisms for treatment selection in mCRC patients.

Purpose of the Study:

  • To assess the utility of TYMS-3'UTR and ERCC1-118C/T polymorphisms in tailoring first-line therapy for mCRC.
  • To compare progression-free survival (PFS) between a control group and an experimental group receiving personalized treatment.

Main Methods:

  • A randomized, open-label phase II trial involving 195 mCRC patients.
  • Control group received bevacizumab plus XELOX.
  • Experimental group received bevacizumab plus FUOX, FUIRI, XELIRI, or XELOX based on TYMS and ERCC1 polymorphisms.

Main Results:

  • The primary endpoint (PFS) was not met; median PFS was 9.4 months (control) vs. 10.1 months (experimental).
  • Overall survival was similar between groups.
  • The experimental group showed a significantly higher overall response rate (ORR) and R0 resection rate, with reduced toxicity.

Conclusions:

  • Treatment personalization based on TYMS and ERCC1 polymorphisms did not improve survival in mCRC.
  • Improved ORR, R0 resection rates, and reduced toxicity suggest potential for further investigation.
  • Tailoring therapy by these polymorphisms warrants further research in mCRC patients.

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