Comparison of mTOR inhibitors combined with endocrine therapy versus that alone in breast cancer: a meta-analysis.

Background: This meta-analysis aims to evaluate the efficacy and safety of rapamycin (mTOR) inhibitors with endocrine therapy versus endocrine therapy alone in treating advanced or metastatic estrogen receptor/progesterone receptor (ER/PR) + breast cancer.

Methods: We conducted a comprehensive search in PubMed, Web of Science, Embase, and the Cochrane Library for randomized controlled trials (RCTs) comparing mTOR inhibitors plus endocrine therapy with endocrine therapy alone up to September 2024.

Results: This analysis included 10 RCTs comprising 3,337 patients. Relative to endocrine therapy alone, the combination of mTOR inhibitors and endocrine therapy significantly improved the clinical benefit rate (RR = 1.41, p < 0.001), overall response rate (RR = 1.40, p = 0.006), progression-free survival (PFS; HR = 0.67, p < 0.001), and overall survival (OS; HR = 0.86, p = 0.056), although the improvement in OS was not statistically significant. Subgroup analyses indicated a more pronounced PFS advantage in patients under 65 years of age (HR = 0.55, p = 0.013) and those who had previously received chemotherapy (HR = 0.51, p = 0.001). However, the incidence of adverse events was higher in the combination therapy group, notably stomatitis (p < 0.001), elevated aspartate aminotransferase/alanine aminotransferase (p = 0.04), and diarrhea (p = 0.01).

Conclusions: The combination of mTOR inhibitors with endocrine therapy offers superior efficacy with manageable toxicities in patients with advanced or metastatic ER/PR+ breast cancer.