Circulating tumor cells as a longitudinal biomarker in patients with advanced chemorefractory, RAS-BRAF wild-type colorectal cancer receiving cetuximab or panitumumab

Valeria Musella, Filippo Pietrantonio, Eleonora Di Buduo, Roberto Iacovelli, Antonia Martinetti, Elisa Sottotetti, Ilaria Bossi, Claudia Maggi, Maria Di Bartolomeo, Filippo De Braud, Maria Grazia Daidone, Vera Cappelletti

Research output: Contribution to journalArticle

Abstract

A still relevant number of patients with RAS-BRAF wild-type colorectal cancer (CRC) do not respond to treatment with antiepidermal growth factor receptor (EGFR) monoclonal antibodies cetuximab and panitumumab, suggesting that additional biomarkers to guide patient selection are urgently needed. Circulating tumor cells (CTCs) may represent such a biomarker. In this prospective study, 38 patients with advanced RAS-BRAF-wild-type CRC received third-line therapy with cetuximab-irinotecan or panitumumab. Peripheral blood samples for CTC status determination were collected at baseline, during treatment at early (2-4 weeks) and at later (8-10 weeks) times. CTC enrichment was done with the AdnaTest ColonCancerSelect kit, whereas CTC detection was done with the AdnaTest ColonCancerDetect kit. CTC status positivity was defined according to the kit manufacturer's thresholds. Fifty percent of patients were defined as CTC positive at baseline and the overall RECIST response rate was 26%. CTC baseline status was not associated with treatment response, whereas early CTC status and CTC status changes during treatment were significantly associated with tumor response. Kaplan-Meier analysis showed a significantly shorter progression-free survival (median, 2.0 versus 4.0 months, p=0.004) and overall survival (4.7 versus11.4, p=0.039) in patients with early CTC+status compared with CTC - ones. In multivariable analysis including classical prognostic factors, the CTC status changes profile during treatment was an independent predictor of both progression-free survival (p

Original languageEnglish
Pages (from-to)1467-1474
Number of pages8
JournalInternational Journal of Cancer
Volume137
Issue number6
DOIs
Publication statusPublished - Sep 1 2015

Keywords

  • biomarker
  • cetuximab
  • circulating tumor cell
  • colorectal cancer
  • panitumumab

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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