A Systematic Review to Evaluate the Corresponding Toxicity and Side Effects of CDK4/6 Inhibitors in Advanced Breast Cancer

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Although it prolongs progression-free survival (PFS) in patients being treated for advanced breast cancer (ABC), the combination of cyclin-dependent kinase (CDK)4/6 inhibitors with endocrine therapy is also associated with toxic side effects. There are only a small number of studies that have previously reviewed the potential toxicity and side effects of CDK4/6 inhibitors in this population.

Therefore, to make fully informed treatment decisions, it is necessary to assess the elevated survival rates associated with treatment with CDK/6 inhibitors and weigh those benefits against the impact of the corresponding toxicity and side effects on patients’ quality of life.

Two independent investigators searched several databases and identified randomized controlled trials involving CDK4/6 inhibitors in combination with endocrine therapy for patients with ABC.

A total of 3685 patients were included from 64 randomized controlled trials. When assessed and compared with placebo combined with endocrine therapy, treatment with CDK4/6 inhibitors combined with endocrine therapy was shown to improve the median PFS rate (hazard ratio, 0.54; 95% confidence interval, 0.50-0.60; P <.00001).

CDK4/6 inhibitors combined with endocrine therapy had higher rates of adverse reactions, including anemia, diarrhea, fatigue, febrile neutropenia, leukopenia, nausea, neutropenia, thrombocytopenia, as well as increased alanine aminotransferase.

In the treatment of patients with ABC, CDK4/6 inhibitors have strong specifications due to their role in regulating the cell cycle. This treatment regimen increases the incidence of adverse reactions, although CDK4/6 inhibitors combined with endocrine therapy can improve the effective rate and median PFS of patients with hormone receptor–positive/HER2-negative ABC. Future studies are warranted to improve patient survival rates while focusing on efforts to mitigate or even prevent the potential side effects of CDK4/6 inhibitors.

Source

Yang L, Xue J, Yang Z, et al. Side effects of CDK4/6 inhibitors in the treatment of HR+/HER2-advanced breast cancer: a systematic review and meta-analysis of randomized controlled trials. Ann Palliat Med. 2021;10:5590-5599.

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