Monitoring circulating tumor cell (CTC) levels to predict rapid progression in metastatic breast cancer (MBC): A prospective, multi-institutional tria

Abstract

509 Background: For patients with MBC, early indication that a chosen therapy is not effective would permit initiation of an alternative regimen. We conducted a prospective, multi-institutional clinical trial to determine if monitoring CTC levels might identify such patients. Methods: 177 patients with measurable MBC about to start a new systemic therapy were enrolled and monitored at 3–4 week intervals for up to six months. CTC were immunomagnetically separated from 7.5 ml whole blood based on EpCAM binding. After multi-color fluorescent labeling, cells were classified by microscopy as CTC if they stained positive for both DAPI and cytokeratin 8,18 and/or 19 and if they stained negative for CD45. Clinical outcomes were determined by the participating clinical sites without knowledge of CTC levels. Results: Data from the first 102 patients were used in a training set to establish that ≥5 CTC/7.5 ml blood at both baseline and 1st follow-up was the optimal cutoff to best distinguish short Progression Free Survival (PFS) and/or Overall Survival (OS). The remaining 75 patients were then used as a validation set. Overall, 87/177 (49%) had ≥5 CTC at baseline, and 49/163 (30%) had persistent or newly elevated levels at 1st follow-up. At baseline, =5CTC/7.5ml was associated with significantly shorter PFS (2.7 vs 7.0 months; p=0.0001) and OS (10.1 vs >18 months, p=0.0001). At 1st follow-up, =5 CTC/7.5ml was associated with very short PFS (2.1 vs. 7.0 months from baseline blood draw; p=0.0001) and OS (8.2 vs. >18 months; p= 0.0001). PFS and OS for patients with a reduction in CTC to <5/7.5ml at 1st follow-up were equivalent to those of patients with <5/7.5ml CTC at baseline. In multi-variate analyses, CTC was the strongest and most significant predictor of poor outcome. Conclusions: Baseline CTC levels are a strong independent predictor of PFS and OS. Importantly, patients with =5 CTC/7.5ml at 1st follow-up appear to be on futile therapy and may benefit from an alternative regimen. A prospective, randomized trial is being designed to test this hypothesis. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Immunicon Corp. Immunicon Corp. Immunicon Corp. Immunicon Corp. Immunicon Corp. Immunicon Corp.