Role of early circulating tumour cell (CTC) monitoring for prediction of clinical outcome in patients with HER-2 negative metastatic breast cancer receiving first-line treatment with bevacizumab and paclitaxel

Abstract

Background Circulating tumor cells (CTC) are associated with clinical outcome in metastatic breast cancer (MBC). We explored the ability of early CTC monitoring (after 2 cycles) for predicting clinical benefit (CB), overall response rate (ORR) and outcome in terms of progression-free survival (PFS) and overall survival (OS) in patients (pts) with HER-2 negative MBC receiving first-line treatment with bevacizumab and paclitaxel. Methods Multicenter prospective observational study. Centralized CTC determination was performed at baseline (C0) and after cycle 2 (C2) using CellSearch. A cutoff of 5 CTCs/7.5ml was used to stratify pts into treatment-sensitive (<5 CTCs) and resistant (≥5 CTCs). The optimal CTC level cutoff for predicting CB and PFS was assessed using ROC curves. Results 111 pts were enrolled: median age: 54 years; ECOG 0/1: 50.5/39.6%; triple-negative: 29%; metastatic sites (median): 3; metastases location: liver (62%), bone (58%), lung (40%). The clinical benefit rate (CBR), ORR, and median PFS for the whole cohort were 65%, 41%, and 16.6 months, respectively. With a median follow-up of 17.5 months, the median OS was not achieved. At C0, 43/87 (49%) and 44/87 (50.6%) pts presented with <5 and ≥5 CTCs, respectively. The CTC level after C2 was in 73/85 (86%) and 12/85 (14%) pts <5 and ≥5, respectively. Among pts with CTCs ≥5 at C0, 78% had <5 CTCs after C2. The CTC level after C2 was predictive for CBR (73% vs 59%, p=0,046), ORR (48% vs 17%, p=0.043), and PFS (17 vs. 5 months, p=0.026). Median OS was 13 months in pts with ≥5 CTCs after C2 and it was not achieved in pts with <5 CTCs (p <0.001). A cutoff point of 1 CTC after C2 yielded 65% sensitivity and 61% specificity for prediction of PFS (p=0.021). Pts with 0 CTC achieved a significantly longer PFS vs. those with at least 1 CTC after 2 cycles (22.6 vs. 8.1 months; p=0.005). Grade 3-4 toxicity rate (39%) was not significantly different according to CTCs after 2 cycles (p =0.531). Conclusions CTC monitoring after 2 cycles of first-line bevacizumab-paclitaxel treatment may predict tumor response and clinical outcome in terms of PFS and OS in HER-2 negative MBC.