title: mTOR inhibitors, a new era for metastatic luminal HER2-negative breast cancer? A systematic review and a meta-analysis of randomized trials.
abstract: 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.
authors.affiliation: Department of Experimental and Clinical Medicine, Medical Oncology, Magna Graecia University, Viale Europa, Catanzaro, Italy.
authors.forename: Maria Saveria
authors.initials: MS
authors.lastname: Rotundo
authors.affiliation: Department of Experimental and Clinical Medicine, Medical Oncology, Magna Graecia University, Viale Europa, Catanzaro, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Galeano
authors.affiliation: Department of Experimental and Clinical Medicine, Translational Medical Oncology, Magna Graecia University, Viale Europa, Catanzaro, Italy.|Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia PA, USA.
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Tassone
authors.affiliation: Department of Experimental and Clinical Medicine, Medical Oncology, Magna Graecia University, Viale Europa, Catanzaro, Italy.
authors.forename: Pierosandro
authors.initials: P
authors.lastname: Tagliaferri
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D006801:Humans; D009362:Neoplasm Metastasis; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D020123:Sirolimus / Q000008:administration & dosage; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013629:Tamoxifen / Q000008:administration & dosage
chemical_list: D018931:Antineoplastic Agents, Hormonal; D018719:Erb-b2 Receptor Tyrosine Kinases; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D013629:Tamoxifen; C546842:MTOR protein, human
keywords: hormonal therapy; luminal breast cancer; mTOR inhibitor; meta-analysis; metastatic breast cancer