P1-06-12: Circulating Tumor Cells (CTC) Monitoring during Phase II Study with Lapatinib (L) and Capecitabine (C) in Patients with Brain Metastases from HER2−Positive (+) Metastatic Breast Cancer (MBC) before Whole Brain Radiotherapy (WBR): LANDSCAPE Study.

Abstract

Abstract Background: Decrease of CTC level during treatment in MBC has been reported as an independent prognostic and predictive factor of patients’ outcome. Monitoring CTC in addition to clinical response criteria is currently evaluated in early clinical trials in various cancer types. We sought to evaluate the clinical interest of peripheral blood CTC for patients included in the LANDSCAPE study which assessed the efficacy of upfront systemic treatment with L+C for newly diagnosed brain metastasis. Methods: This analysis is a preplanned secondary endpoint of the LANDSCAPE study. Eligible pts had HER2+ MBC with BM not previously treated with WBR, C or L. Pts received L1250 mg/day and C2000 mg/m2/day, days 1–14, every 21 days. The primary endpoint was a centrally assessed CNS objective response (CNS-OR) defined as a ≥50% volumetric reduction of CNS lesions in the absence of increasing steroid use, progressive neurologic symptoms or progressive extra-CNS disease. CTC were detected in 7.5 ml of blood using the CellSearchSystem™, combining EpCAM immunomagnetic selection (IMS) followed by anti-cytokeratin (A45B/B3) fluorescently staining for CTC at baseline and at day (D) 21, before cycle 2. Results: From 04/2009 to 08/2010, 45 pts were enrolled, 41 were evaluable for CTC at baseline and 38 at D21. Median age was 56 (range 35 to 79). PS was >1 only in 2 pts. At baseline, 20/41 (48.8%) pts had ≥ 1CTC and 9 (22%) ≥ 5CTC (range 1–301, median 3). CTC were detected in pts with (18/37) or without disease outside SNC (2/6) (p=0.63). At a median follow-up of 10 months (range 2.9−16.5), median TTP was 6.0 months [95% CI 4.9; 7.4] vs. 4.3 [2.8; 5.9] months for pts without and with CTC at baseline respectively (p=0.14). After 21 days of treatment, a disappearance of CTC was observed in 11pts (31%). At D21, only 7 (18.4%) pts had ≥ 1CTC and 3 (8%) ≥ 5 CTC (p=0.006, D21 vs. baseline). In 43 evaluable pts, CNS-OR rate was 67% (95%CI 51–81), with a median time from inclusion to response of 1.8 month. Absence of CTC was not correlated with CNS-OR rate at baseline (17/21 (81%) vs. 11/19 (58%), NS). Strikingly, remaining positivity for CTC at D 21 (≥ 1CTC) was correlated with a poor response rate in CNS: 2/6 (33.3%) vs. 25/31 (80.6%) in pts with 0 CTC, p=0.03. Conclusions: Early decrease (at D 21) in CTC level is correlated with a high response rate in newly diagnosed BM to L + C and underlines the predictive value of this blood marker in MBC pts even for brain metastasis. Longer follow-up is needed to assess its prognostic value under antiHER2 targeted therapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-06-12.