Efficacy and safety of CDK4/6 and PI3K/AKT/mTOR inhibitors as second-line treatment in postmenopausal patients with hormone receptor-positive, HER-2-negative metastatic breast cancer: a network meta-analysis.

Background: We compared the efficacy and safety of combinations of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors and PI3K/AKT/mTOR inhibitors as second-line treatment in postmenopausal women with HR, HER2 metastatic breast cancer.

Methods: We searched the Medline, Embase, and Cochrane Library electronic databases for phase II/III randomized trials evaluating CDK4/6 and PI3K/AKT/mTOR inhibitors plus fulvestrant. We compared the results with a network meta-analysis. Study quality was assessed following the GRADE approach. Outcomes of interest were progression-free survival, overall response rate, overall survival and G3-4 adverse drug events (ADEs).

Results: Eight RCTs were identified in the network meta-analysis. PFS was significantly improved by treatment with abemaciclib plus fulvestrant and ribociclib plus fulvestrant compared to pictilisib plus fulvestrant. The ORR following treatment with abemaciclib plus fulvestrant, ribociclib plus fulvestrant, palbociclib plus fulvestrant, buparlisib plus fulvestrant, and alpelisib plus fulvestrant significantly differed from that observed following treatment with placebo plus fulvestrant. In terms of OS, compared with placebo plus fulvestrant, abemaciclib plus fulvestrant, ribociclib plus fulvestrant, and buparlisib plus fulvestrant had a significant difference. The risks of ADEs were similar among three CDK4/6 inhibitors.

Conclusion: As second-line treatment, three CDK4/6 inhibitors showed superior clinical efficacy compared to other PI3K/AKT/mTOR inhibitors with comparable safety profiles.