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

Yannan Zhao, Fangfang Lv, She Chen, Zhonghua Wang, Jian Zhang, Sheng Zhang, Jun Cao, Leiping Wang, Enying Cao, Biyun Wang, Xichun Hu, Yannan Zhao, Fangfang Lv, She Chen, Zhonghua Wang, Jian Zhang, Sheng Zhang, Jun Cao, Leiping Wang, Enying Cao, Biyun Wang, Xichun Hu

Abstract

Background: Nanoparticle 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.

Methods: Nab-paclitaxel (125 mg/m2) and gemcitabine (800 mg/m2) were administered on days 1, 8, and 15 in a 4-week cycle. 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.

Results: Among 85 patients enrolled in the study, ORR was 52.4%. After a median follow-up of 17.2 months, median PFS was 7.9 months (95%CI, 6.6-9.2) and median OS was 25.8 months (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.

Conclusions: The 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 registration: NCT01550848 . Registered 12 March 2012.

Keywords: Caveolin-1; Chemotherapy; Gemcitabine; Metastatic breast cancer; Nab-paclitaxel.

Conflict of interest statement

Ethics approval and consent to participate

Study procedures were approved by the Ethics Committee and Institutional Review Board of Fudan University Shanghai Cancer Center on Nov 28, 2011 (reference No.1111104–8). All patients provided written informed consent prior to any study-related procedures.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flowchart of phase II trial of nab-paclitaxel and gemcitabine
Fig. 2
Fig. 2
Kaplan–Meier curves for progression-free survival. a For patients stratified by lines of therapy. b For patients stratified by prior taxane. Abbreviations: CI, confidence interval; PFS, progression-free survival
Fig. 3
Fig. 3
Kaplan–Meier curves for overall survival. a For patients stratified by lines of therapy. b For patients stratified by prior taxane. Abbreviations: CI, confidence interval; OS, overall survival
Fig. 4
Fig. 4
Representative immunohistochemistry images for patients with tumor/stromal Cav-1 staining. a Tumor exhibited strong intensity (3), moderate intensity (2), weak intensity (1) and negative (0) for Cav-1 (from right panel to left panel). b Stromal exhibited strong intensity (3), moderate intensity (2), weak intensity (1) and negative (0) for Cav-1 (from right panel to left panel). Abbreviations: Cav-1, Caveolin-1
Fig. 5
Fig. 5
Kaplan–Meier curves for progression-free survival in patients with tumor/stromal Cav-1 staining. a For patients stratified by tumor Cav-1 staining. b For patients stratified by stromal Cav-1 staining. c For patients stratified by tumor and stromal Cav-1 staining. Abbreviations: CI, confidence interval; PFS, progression-free survival

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