Modulation and prognostic value of epidermal growth factor receptor (EGFR) expression in circulating tumor cells (CTCs) during chemotherapy (CT) in patients with metastatic colorectal cancer

Abstract

15038 Background: EGFR expression, usually determined on primary tumour specimens, may be altered by confounding factors including chemotherapy (CT) administration. We have evaluated the impact of CT on the EGFR expression of CTCs in comparison to the primary tumor EGFR status. Methods: 7.5 ml of peripheral blood were prospectively collected from chemo-naive patients with metastatic colorectal cancer (mCRC) initiating first-line CT at baseline, before the second cycle, and after four CT cycles.CTCs were detected by using immuno-magnetic separation and immuno-fluorescent identification (Cell Search System, Veridex). The EGFR status in CTCs was determined by immuno-fluorescent labelling. A retrospective evaluation of EGFR expression in the corresponding primary paraffin- embedded tumors was performed with immuno-histochemistry using the Dako Pharm Dx Kit. Results: 22 patients were evaluated: 13 patients received 5-fluorouracil (5-FU), folinic acid (FA), oxaliplatin (FOLFOX), 4 patients FOLFOX + panitumumab; and 5 patients 5- FU+FA+irinotecan. Nine patients (41%) experienced partial response, 7 (32%) stable disease and 6 (27%) progression a progressive disease after 4 cycles of CT. The median storage time of the primitive tumor was 6 weeks (range: 4–8). Fourteen (64%) patients had positive EGFR CTCs at baseline (median 9, range 1–36). On an individual basis, no correlation was found between the EGFR status of the primitive tumour and baseline CTCs (Spearman's correlation: r 0.122; p=0.599). The EGFR status modifications during CT and the predictive value of baseline CTCs EGFR expression in CTCs are reported here. Conclusions: CT administration induces changes in the EGFR status of CTCs. EGFR negative tumours should be retested for EGFR after CT, before initiating anti-EGFR treatment. The EGFR expression of CTCs in mCRC could be useful in predicting outcome under CT and deserves further evaluation. EGFR status modific Baseline CTCs EGFR -ations during CT and predictive value of baseline CTCs EGFR expression Baseline CTCs EGFR + Baseline CTCs EGFR - Patients (N) 14 8 CTCs EGFR+ after 1 cycle CT 14 6 CTCs EGFR + after 4 cycles CT 13 7 Median time to progression (months) 6.6 (confidence interval : 4–8.2) 8.5 (confidence interval : 7.5–9.5) Log rank test p = 0.04 No significant financial relationships to disclose.