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 nonvisceral (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.

Endocrine‐based treatments in clinically‐relevant subgroups of hormone receptor‐positive/HER2‐negative metastatic breast cancer: systematic review and meta‐analysis

Venturini, Sergio;Rognoni, Carla;Generali, Daniele
2021

Abstract

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 nonvisceral (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.
2021
2021
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
File in questo prodotto:
File Dimensione Formato  
cancers-13-01458.pdf

accesso aperto

Descrizione: articolo
Tipologia: Pdf editoriale (Publisher's layout)
Licenza: Creative commons
Dimensione 1.37 MB
Formato Adobe PDF
1.37 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11565/4037490
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 16
  • ???jsp.display-item.citation.isi??? 14
social impact