Caveolin-1 expression predicts efficacy of weekly nab-paclitaxel plus gemcitabine for metastatic breast cancer in the phase II clinical trial

BackgroundNanoparticle albumin-bound (nab)-paclitaxel has better efficacy, safety profiles, and no need to use prophylactic steroids compared with solvent-based paclitaxel. We performed a single arm, phase II study to evaluate the efficacy and safety of weekly nab-paclitaxel and gemcitabine combination in patients with metastatic breast cancer (MBC) and explored role of tumor/stromal Caveolin-1 (Cav-1) as a predictive biomarker for the efficacy.MethodsNab-paclitaxel (125mg/m(2)) and gemcitabine (800mg/m(2)) were administered on days 1, 8, and 15 in a 4-weekcycle. The primary end point was objective response rate (ORR). Secondary end points were progression free survival (PFS), overall survival (OS) and safety profile. Exploratory study included immunohistochemical detection of Cav-1.ResultsAmong 85 patients enrolled in the study, ORR was 52.4%. After a median follow-up of 17.2months, median PFS was 7.9months (95%CI, 6.6-9.2) and median OS was 25.8months (95% CI, 20.4-31.1). The most common toxicities were neutropenia (75.0% for all grades; 45.2% for grade 3 or worse) and the most common non-hematologic toxicity was peripheral neuropathy (50.0% for all grades, 7.14% for grade 3 or worse). Higher tumor Cav-1 level and lower stromal Cav-1 level were significantly associated with longer PFS of nab-paclitaxel and gemcitabine.ConclusionsThe regimen had substantial antitumor activity and was well tolerated in MBC patients. Tumor/stromal Cav-1 level may be a good predictor for the efficacy of nab-paclitaxel and gemcitabine.Trial registrationNCT01550848. Registered 12 March 2012.