Journal
EXPERT OPINION ON DRUG SAFETY
Volume 20, Issue 8, Pages 949-957Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/14740338.2021.1931116
Keywords
CDK4; 6 inhibitors; PI3k; Akt; mTOR inhibitors; second-line treatment; hormone receptor-positive; HER-2-negative; metastatic breast cancer; network meta-analysis
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Funding
- An Nan Hospital, China Medical University research fund
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In postmenopausal women with HR+, HER2(-) metastatic breast cancer, combinations of CDK4/6 inhibitors and PI3K/AKT/mTOR inhibitors showed superior clinical efficacy as second-line treatment, with abemaciclib and ribociclib plus fulvestrant significantly improving progression-free survival (PFS) compared to other combinations. However, the safety profiles of all three CDK4/6 inhibitors were comparable.
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.
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