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

ABSTRACT

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.

KEYWORDS:

• CDK4/6 inhibitors
• PI3k/Akt/mTOR inhibitors
• second-line treatment
• hormone receptor-positive
• HER-2-negative
• metastatic breast cancer
• network meta-analysis

Supplemental data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2021.1931116.

Author contributions

Conceptualization: Agnes Chan. Data curation: John Hang Leung. Formal analysis: Henry WC Leung. Methodology: Agnes Chan, Shyh-Yau Wang. Software: John Hang Leung, Agnes Chan.Writing – original draft: Agnes Chan, Song-Shan Huang.Writing – review & editing: Song-Shan Huang, Henry WC Leung.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This study was supported by the An Nan Hospital, China Medical University research fund.