Research Papers:

mTOR inhibitors, a new era for metastatic luminal HER2-negative breast cancer? A systematic review and a meta-analysis of randomized trials

Maria Saveria Rotundo _, Teresa Galeano, Pierfrancesco Tassone and Pierosandro Tagliaferri

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Oncotarget. 2016; 7:27055-27066. https://doi.org/10.18632/oncotarget.7446

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Maria Saveria Rotundo1, Teresa Galeano1, Pierfrancesco Tassone2,3, Pierosandro Tagliaferri1

1Department of Experimental and Clinical Medicine, Medical Oncology, Magna Graecia University, Viale Europa, and Catanzaro, Italy

2Department of Experimental and Clinical Medicine, Translational Medical Oncology, Magna Graecia University, Viale Europa, Catanzaro, Italy

3Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia PA, USA

Correspondence to:

Pierosandro Tagliaferri, e-mail: [email protected]

Keywords: metastatic breast cancer, luminal breast cancer, meta-analysis, hormonal therapy, mTOR inhibitor

Received: November 02, 2015    Accepted: January 29, 2016    Published: February 17, 2016


We evaluated if standard hormonal therapy (HT) could be improved by the addition of mammalian target of rapamycin inhibitors (mTOR-I) in metastatic luminal breast cancer. A meta-analysis on 4 phase II-III randomized clinical trials was performed. Pooled hazard ratio (HR) for progression free survival (PFS)/ time to progression (TTP) was 0.62 in favor of mTOR-I+HT arm (95% confidence interval [CI] 0.55-0.70; p<0.0001). There was significant heterogeneity for PFS/TTP (Cochran’s Q 32, p<0.0001, I2 index 90.6%). Pooled HR for overall survival (OS) was 0.84 in favor of the combination arm (95% CI 0.71-0.99; p=0.04). Heterogeneity was not significant (Cochran’s Q 4.47, p=0.1, I2 index 55.3%). Pooled risk ratio (RR) for objective response rate (ORR) was 0.88 in favor of experimental arm (95% CI 0.85-0.91; p<0.0001). Heterogeneity was not significant (Cochran’s Q 2.11, p=0.3, I2 index 5.2%). Adverse events (AEs), in particular those of grade 3-4, mostly occurred in mTOR-I+HT arm. Combination therapy of HT plus mTOR-I improves the outcome of metastatic luminal breast cancer patients. Our results provide evidence of a class-effect of these targeting molecules.

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