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.
Endocrine‐based treatments in clinically‐relevant subgroups of hormone receptor‐positive/her2‐negative metastatic breast cancer: Systematic review and meta‐analysis / Schettini, F.; Giuliano, M.; Giudici, F.; Conte, B.; De Placido, P.; Venturini, S.; Rognoni, C.; Leo, A. D.; Locci, M.; Jerusalem, G.; Mastro, L. D.; Puglisi, F.; Conte, P.; De Laurentiis, M.; Pusztai, L.; Rimawi, M. F.; Schiff, R.; Arpino, G.; De Placido, S.; Prat, A.; Generali, D.. - In: CANCERS. - ISSN 2072-6694. - 13:6(2021), pp. 1-21. [10.3390/cancers13061458]
Endocrine‐based treatments in clinically‐relevant subgroups of hormone receptor‐positive/her2‐negative metastatic breast cancer: Systematic review and meta‐analysis
Schettini F.;Giuliano M.;De Placido P.;Locci M.;De Laurentiis M.;Arpino G.;De Placido S.;
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 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
