Endocrine-Based Treatments in Clinically-Relevant Subgroups of Hormone Receptor-Positive/HER2-Negative Metastatic Breast Cancer: Systematic Review and Meta-Analysis

• Published in: Cancers Vol. 13; no. 6; p. 1458
• Main Authors: Schettini, Francesco, Giuliano, Mario, Giudici, Fabiola, Conte, Benedetta, De Placido, Pietro, Venturini, Sergio, Rognoni, Carla, Di Leo, Angelo, Locci, Mariavittoria, Jerusalem, Guy, Del Mastro, Lucia, Puglisi, Fabio, Conte, PierFranco, De Laurentiis, Michelino, Pusztai, Lajos, Rimawi, Mothaffar F, Schiff, Rachel, Arpino, Grazia, De Placido, Sabino, Prat, Aleix, Generali, Daniele
• Format: Journal Article Web Resource
• Language: English
• Published: Switzerland Multidisciplinary Digital Publishing Institute (MDPI) 22.03.2021; MDPI
• Subjects: endocrine therapy; hormone receptor; Human health sciences; meta-analysis; metastatic breast cancer; Oncologie; Oncology; Sciences de la santé humaine; Systematic Review; meta-analysis; hormone receptor; systematic review; metastatic breast cancer; endocrine therapy
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers13061458

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 ( = 0.63) and endocrine sensitive disease ( = 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.