PD-0011 - Circulating tumor cells (CTCs) as prognostic biomarker in patients with advanced chemorefractory, RAS wild-type colorectal cancer (CRC) treated with...

Date 27 June 2014
Event World GI 2014
Session Poster discussion session II – Tumor burden and biomarkers
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Translational Research
Presenter V. Musella
Citation Annals of Oncology (2014) 25 (suppl_2): ii5-ii13. 10.1093/annonc/mdu164
Authors V. Musella1, E. Di Buduo2, A. Martinetti2, E. Sottotetti3, V. Cappelletti3
  • 1Fondazione IRCCS Istituto Nazionale dei Tumori, Milano/IT
  • 2Fondazione IRCCS Istituto Nazionale dei Tumori, Milan/IT
  • 3Fondazione IRCSS Istituto Nazionale dei Tumori, Milan/IT

Abstract

Introduction

Anti-EGFR monoclonal antibodies (MoAb) cetuximab and panitumumab improved outcome of patients with advanced RAS wild-type CRC in combination with chemotherapy or in chemorefractory disease. Even in molecularly enriched populations, additional biomarkers to drive “negative” selection of patients are urgently needed to identify the relevant subset of non responders. CTCs may represent useful real time liquid biopsy. A meta-analysis demonstrated that CTCs+ CRC patients treated with chemotherapy have 2-fold increased risk of progressive disease (PD) and 2.5-fold increased risk of death. In this study, we aimed at identifying the prognostic role of CTCs at baseline and their modulation by anti-EGFR MoAb in patients with advanced chemorefractory, RAS wild-type CRC.

Methods

This was a prospective, monocentric, observational study approved by the Institutional Review Board of Fondazione IRCCS Istituto Nazionale dei Tumori. Main inclusion criteria: advanced RAS wild-type CRC; measurable disease (RECIST 1.1); treatment with cetuximab-irinotecan or panitumumab after failure of standard chemotherapy including fluoropyrimidines, oxaliplatin and irinotecan; written informed consent.

Five peripheral blood samples (5 ml of whole blood collected in K3 EDTA tubes) were collected at baseline, early at 2-4 weeks from treatment start and every 8-10 weeks from treatment start (concomitantly with CT scans). To investigate a potential predictive value, besides time-points CTCs status, the CTCs modulation profile was defined as unfavourable profile (CTCs + /- at baseline, but CTC+ at early and/or first reassessment time-points) vs. favourable profile (CTC + /- at baseline, but CTC- at early assessment and confirmed in 2 subsequent samples). CTCs were isolated within 1 hour from blood withdrawal using the AdnaGEN Colon Select kit and detected with the AdnaGEN colon Detect kit. Samples were defined as CTC+ if at least one of genes evaluated by RTPCR on CTC lysates (EGFR, EPCAM, CEA) was above the commercially defined thresholds. Investigators responsible of clinical or laboratory data were reciprocally blinded.

Results

Thirty-eight patients were prospectively enrolled from July 2012 to October 2013. Overall, response rate and disease control rate were 26% and 40%, respectively. At a median follow up of 14.7 months, mPFS and mOS were 2.8 and 7.6 months. At baseline, outcomes were not significantly different when comparing CTC+ vs. CTC- pts (mPFS: 3.2 vs. 2.7 months, p = 0.938; median OS 6.1 vs. 10.1 months, p = 0.23). Patients defined as CTC+ after 2-4 weeks from treatment start had a significantly shorter mPFS vs. those CTC- (2.0 vs. 3.5 months; HR = 1.7, 95%CI 1.23-2.18; p = 0.0029) and a trend towards decreased mOS (5.5 vs. 10.0 months; HR = 1.81, 95%CI 1.41-2.22; p = 0.06). Patients with unfavourable CTCs profile had significantly shorter mFS (2.0 vs. 5.0 months; HR 2.5, 95%CI 2.01-2.98; p = 0.0008) and mOS (4.7 months vs. not reached; p = 0.0004).

Conclusion

This is the first study investigating the prognostic role of CTCs in patients receiving anti-EGFR MoAb as ≥ 3rd treatment line for RAS wild-type CRC. Interestingly, CTCs status evaluated at baseline does not seem to be prognostic in chemorefractory CRC, while early CTCs assessment or their modulation during treatment predicts outcomes. Clinically valuable information can be obtained from CTC modulations during treatment.