Abstract 310P
Background
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i), in combination with endocrine therapy (ET), have been recommended as standard therapeutic strategies in hormone receptor-positive (HR+), human epidermal growth factor receptor type 2-negative (Her2-) advanced breast cancer (ABC). Previous studies have confirmed progression-free survival (PFS) benefits with CDK4/6i plus ET, however, whether the addition of CDK4/6i to ET can provide overall survival (OS) improvements remains controversial. This study aimed to further assess the long-term efficacy and safety of CDK4/6i in HR+, Her2- ABC patients and find the suitable subject population for CDK4/6i by subgroup analysis.
Methods
Electronic literature databases (MEDLINE, EMBASE and Cochrane) were searched for relevant randomized controlled trials (RCTs) published from Jan 2014 to Jan 2020. In addition, abstracts and presentations from all major conference proceedings were reviewed. All RCTs that compared the efficacy and safety of CDK4/6i plus ET with ET alone in HR+, Her2- ABC were selected. The pooled analyses of hazard ratios (HRs) for PFS and OS, and risk ratios (RRs) for objective response rates (ORRs) and adverse events (AEs) were obtained by Stata or Revman software with the random-effects model.
Results
A total of 8 RCTs and 4580 HR+, Her2- ABC patients were enrolled in this study. The pooled HR for OS was 0.76 (95% CI: 0.67–0.84), and the pooled HR for PFS was 0.55 (95% CI:0.50–0.59). Improvements in OS and PFS were consistent among subgroup analysis of drugs, treatment lines, age distribution, races, PR status, menopausal status, metastatic sites and endocrine resistant status. Moreover, CDK4/6i meaningfully improved ORR both in intention-to-treat population (RR=1.47; 95% CI:1.29–1.67) and patients with measurable disease (RR=1.47; 95% CI:1.30–1.67), and increased the incidence of grade 3/4 AEs (RR=2.69; 95% CI:2.43–2.97).
Conclusions
The combination of CDK4/6i and ET was superior to ET alone in terms of OS and PFS, regardless of drugs, treatment lines, age distribution, races, PR status, menopausal status, metastatic sites and endocrine resistant status. More mature OS results are awaited to consolidate our study.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.