Endocrine-Based Treatments in Clinically-Relevant Subgroups of Hormone Receptor-Positive/HER2-Negative Metastatic Breast Cancer: Systematic Review and Meta-Analysis
endocrine therapy; hormone receptor; meta-analysis; metastatic breast cancer; systematic review
Abstract :
[en] A precise assessment of the efficacy of first-/second-line endocrine therapies (ET) ± target therapies (TT) in clinically-relevant subgroups of hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (MBC) has not yet been conducted. To improve our current knowledge and support clinical decision-making, we thus conducted a systematic literature search to identify all first-/second-line phase II/III randomized clinical trials (RCT) of currently approved or most promising ET ± TT. Then, we performed a meta-analysis to assess progression-free (PFS) and/or overall survival (OS) benefit in several clinically-relevant prespecified subgroups. Thirty-five RCT were included (17,595 patients). Pooled results show significant reductions in the risk of relapse or death of 26-41% and 12-27%, respectively, depending on the clinical subgroup. Combination strategies proved to be more effective than single-agent ET (PFS hazard ratio (HR) range for combinations: 0.60-0.65 vs. HR range for single agent ET: 0.59-1.37; OS HR range for combinations: 0.74-0.87 vs. HR range for single agent ET: 0.68-0.98), with CDK4/6-inhibitors(i) + ET being the most effective regimen. Single agent ET showed comparable efficacy with ET+TT combinations in non-visceral (p = 0.63) and endocrine sensitive disease (p = 0.79), while mTORi-based combinations proved to be a valid therapeutic option in endocrine-resistant tumors, as well as PI3Ki + ET in PIK3CA-mutant tumors. These results strengthen international treatment guidelines and can aid therapeutic decision-making.
Disciplines :
Oncology
Author, co-author :
Schettini, Francesco; University of Naples > Department of clinical medicine and surgery
Giuliano, Mario; University of Naples > Department of clinical medicine and surgery
Giudici, Fabiola; University of Padova > Department of Cardiac,Thoracic,Vascular Sciences and Public Health
Conte, Benedetta; IDIBAPS, Barcelona, Spain > Translational Genomics and Targeted Therapies in Solid Tumors
De Placido, Pietro; University of Naples Frederico II, Italy > Department of Clinical Medicine and Surgery
Venturini, Sergio; University of Turin, Italy > Department of Management
Rognoni, Carla; SDA Bocconi School of Management, Milan, Italy > Centre for Research on Health and Social Care Management
Di Leo, Angelo; Hospital of Prato, Italy > "Sandro Pitigliani" Medical Oncology Department
Locci, Mariavittoria; University of Naples Federico II, Italy > Department of Neuroscience, Reproductive Medicine and Odontostomatological Sciences
Jerusalem, Guy ; Université de Liège - ULiège > Medical Oncology Department > Oncologie médicale
Del Mastro, Lucia; IRCCS Ospedale Policlinico San Martino, Genoa, Italy > Breast Unit
Puglisi, Fabio; University of Udine, Italy > Department of Medicine
Conte, PierFranco; University of Padova, Italy > Department of Surgery, Oncology and Gastroenterology
De Laurentiis, Michelino; INT-Fondazione "G. Pascale", Naples, Italy > Breast Oncology Unit
Pusztai, Lajos; Yale University School of Medicine, New Haven, USA > Department of Medicine
Rinmawi, Mothaffar F.; Baylor College of Medicine, Houston, USA > Dan L. Duncan Comprehensive Cancer Center
Schiff, Rachel; Baylor College of Medecine, Houston, USA > Department of Medicine
Arpino, Grazia; University of Naples, "Federico II", Naples, Italy > Department of Clinical Medicine and Surgery
De Placido, Sabino; University of Naples "Federico II", Naples, Italy > Department of Clinical Medicine and Surgery
Prat, Aleix; IDIBAPS, Barcelona, Spain > Translational Genomics and Targeted Therapies in Solid Tumors
Generali, Daniele; University of Trieste, Italy > Department of Medical, Surgery and Health Sciences
Endocrine-Based Treatments in Clinically-Relevant Subgroups of Hormone Receptor-Positive/HER2-Negative Metastatic Breast Cancer: Systematic Review and Meta-Analysis
Publication date :
2021
Journal title :
Cancers
eISSN :
2072-6694
Publisher :
Multidisciplinary Digital Publishing Institute (MDPI), Switzerland
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