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.

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., Endocrine‐based treatments in clinically‐relevant subgroups of hormone receptor‐positive/her2‐negative metastatic breast cancer: Systematic review and meta‐analysis, <<CANCERS>>, 2021; 13 (6): 1-21. [doi:10.3390/cancers13061458] [https://hdl.handle.net/10807/238857]

Endocrine‐based treatments in clinically‐relevant subgroups of hormone receptor‐positive/her2‐negative metastatic breast cancer: Systematic review and meta‐analysis

Venturini, Sergio;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 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.
2021
Inglese
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., Endocrine‐based treatments in clinically‐relevant subgroups of hormone receptor‐positive/her2‐negative metastatic breast cancer: Systematic review and meta‐analysis, <<CANCERS>>, 2021; 13 (6): 1-21. [doi:10.3390/cancers13061458] [https://hdl.handle.net/10807/238857]
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