A subgroup analysis of a large multicenter study Circulating tumor cells, progression-free survival, and overall survival in metastatic colorectal cancer: A subgroup analysis of a large multicenter study Abstract #299 SJ Cohen1, CJA Punt2, N Iannotti3, BH Saidman4, KD Sabbath5, MC Miller6, GV Doyle6, H Tissing6, LWMM Terstappen6, NJ Meropol1 1Fox Chase Cancer Center, Philadelphia, PA; 2Radboud University Medical Center, Nijmegen, The Netherlands; 3Hematology Oncology Associates, Port St Lucie, FL; 4Medical Oncology Associates, Kingston, PA; 5Medical Oncology and Hematology, PC, Waterbury, CT; 6Immunicon Corporation, Huntingdon Valley, PA ABSTRACT We recently demonstrated that circulating tumor cell (CTC) number at baseline and during therapy is an independent prognostic factor for progression-free survival (PFS) and overall survival (OS) for patients with metastatic colorectal cancer (mCRC) beginning a new line of systemic therapy (Meropol ASCO, 2007). The current analysis was undertaken to evaluate the relationship of pre-treatment CTC number with outcome by treatment line, type, and important clinical characteristics. Methods In this prospective multi-center study, 7.5 mL of blood from 430 patients with mCRC were tested for CTC using immunomagnetic separation before starting 1st, 2nd or 3rd line therapy and at follow-up timepoints. Response by imaging was determined by participating investigators. Results Patients were stratified into unfavorable and favorable prognostic groups based on pre-treatment levels of ≥3 or <3 CTC per 7.5mL, respectively. Median PFS, OS and significance between the two groups at baseline (log rank test) by clinical characteristic are indicated in the table. Conclusions CTC levels before treatment are an independent predictor of PFS and OS in patients with mCRC regardless of line of therapy, type of therapy, or clinical characteristics. RESULTS PFS and OS by type of therapy OS by Age HR=2.45 (1.53-3.92) HR=2.07 (1.34-3.2) HR=2.84 (1.9-4.23) HR=1.32 (0.93-1.88) BACKGROUND & OBJECTIVES We demonstrated at ASCO, 2007 that CTC number at baseline and during treatment is an independent predictor of PFS and OS in patients with mCRC (Meropol et al, ASCO, 2007). Patients in that trial had blood drawn at baseline and subsequent intervals for CTC enumeration. Patients evaluable in that trial were heterogeneous (n=430): Receiving any new 1st, 2nd, or 3rd line therapy We thus performed this secondary analysis to evaluate the relationship of baseline CTC number to PFS and OS by treatment line, type, and clinical characteristics. PFS by line of therapy PFS by ECOG PS HR=2.67 (1.62-4.41) HR=2.00 (1.32-3.04) HR=1.34 (0.97-1.87) HR=1.44 (1.04-1.98) HR=2.51 (1.61-3.9) HR=1.90 (1.26-2.85) PFS and OS for all patients – ASCO, 2007 OS by line of therapy OS by ECOG PS HR=2.08 (1.37-2.1) HR=1.5 (1.07-2.1) HR=5.08 (3.02-8.54) HR=1.61 (1.09-2.37) HR=2.22 (1.49-3.30) HR=2.98 (1.85-4.77) MATERIALS & METHODS CTC Sample Preparation on CellTracks® AutoPrep System PFS by Age CONCLUSION CTC levels before treatment predict OS regardless of: treatment line treatment type clinical characteristics CTC levels before treatment predict PFS in nearly all patient subgroups. Further study of CTC as a marker of treatment effect is warranted. PFS and OS with liver involvement HR=1.36 (0.95-1.95) HR=2.25 (1.57-3.23) HR=2.52 (1.79-3.53) HR=1.7 (1.28-2.25)