281P - Cyclin-dependent kinase 4/6 inhibitors combined with endocrine therapy for hormonal receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer: A meta-analysis of randomized clinical trials

Background

The use of cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors combined with endocrine therapy (ET) has recently emerged in the early stages breast cancer (eBC) treatment landscape. The present analysis aims to clarify the efficacy and safety of this treatment for hormonal receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER-) patients in the early stages of breast cancer (eBC).

Methods

PubMed, Scopus, Web of Science, Cochrane, and the Central Register of Clinical Trials were systematically searched for studies using CDK4/6 inhibitors with ET in patients with HR+/HER- early breast cancer (I-IIIA stage). For the meta-analysis, statistical analysis was performed using RStudio v 4.4.2. Heterogeneity was examined with Cochran Q test and I² statistics and p-values inferior to 0.10 and I>25% were considered significant for heterogeneity. The p-value< 0.05 was considered statistically significant.

Results

This study included 9345 patients from six randomized clinical trials. Ductal (87%) and lobular (10%) were the most common, and 53% of women were postmenopausal. Lymph node status data revealed that 9% had N0 status, 72% had N1 status, and 19% had ≥ N2 status. In a pooled analysis, the invasive disease free survival (iDFS) was 82% (95% CI, 0.64-1.06), and the overall survival rates were consistent across the studies, with 12-month rates at 1.00 (95% CI 0.99-1.01), 24-month rates at 1.00 (95% CI 0.99-1.01), 36-month rates at 1.01 (95% CI 0.93-1.10), and 48-month rates at 1.04 (95% CI 0.91-1.19). The most common treatment-related adverse events (AE) included neutropenia (78.1%), leukopenia (51.6%), fatigue (37.6%), diarrhea (31.4%), anemia (30.5%), and arthralgia (29.3%). Any grade 3 adverse events were observed in 2.44 (95% CI 0.84-7.08) and grade 4 in 1.39 (95% CI 0.15-12.68).

Conclusions

This meta-analysis reinforces the antitumor activity of the combination of CDK4/6is with ET in patients with eBC, regardless of iDFS rate. Despite high rates of serious adverse events related to treatment, most were manageable.

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.