1. 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 ( )
HR=2.07 ( )
HR=2.84 ( )
HR=1.32 ( )
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 ( )
HR=2.00 ( )
HR=1.34 ( )
HR=1.44 ( )
HR=2.51 ( )
HR=1.90 ( )
PFS and OS for all patients – ASCO, 2007
OS by line of therapy
OS by ECOG PS
HR=2.08 ( )
HR=1.5 ( )
HR=5.08 ( )
HR=1.61 ( )
HR=2.22 ( )
HR=2.98 ( )
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 ( )
HR=2.25 ( )
HR=2.52 ( )
HR=1.7 ( )