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CDK4/6 Inhibitors as Adjuvant Treatment for Hormone Receptor-Positive/HER2-Negative Early Breast Cancer: A Meta-Analysis

A systematic review and meta-analysis evaluates the efficacy and safety of adding CDK4/6 inhibitors to adjuvant endocrine therapy for hormone receptor-positive/HER2-negative early breast cancer, showing a trend towards improved invasive disease-free survival but no significant benefit in distant relapse-free survival, alongside increased adverse events.

Breast cancer (BC) is the most frequent malignancy among women worldwide, with hormone receptor-positive/HER2-negative (HR+/HER2−) BC being the most common subtype. Despite adjuvant endocrine therapy (ET) reducing recurrence and death risks, up to 20% of patients with early BC (EBC) experience recurrences within 10 years post-surgery. CDK4/6 inhibitors (CDK4/6is) have been approved for HR+/HER2− locally advanced and metastatic BCs, prompting studies on their efficacy in earlier treatment lines.
This meta-analysis reviewed randomized controlled studies comparing CDK4/6is plus ET versus ET alone in HR+/HER2− EBC patients, focusing on invasive disease-free survival (IDFS) as the primary endpoint. Secondary endpoints included distant relapse-free survival (DRFS), adverse events (AEs) incidence, and early treatment discontinuation due to toxicities.
Results from three eligible studies (PALLAS, monarchE, and PENELOPE-B) involving 12,647 patients showed a trend towards IDFS benefit with CDK4/6is (HR 0.85, 95% CI 0.71-1.01; P = 0.071), but no significant DRFS improvement. CDK4/6is were associated with increased AEs incidence and higher risk of early treatment discontinuation due to AEs. The analysis underscores the need for longer follow-up and better patient selection in future trials to clarify CDK4/6is' role in adjuvant settings and their impact on patients' quality of life and healthcare systems.
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Reference News

[1]
CDK4/6 inhibitors as adjuvant treatment for hormone ...
pmc.ncbi.nlm.nih.gov · Mar 18, 2021

Breast cancer, particularly HR+/HER2− subtype, is prevalent among women. Adjuvant endocrine therapy reduces recurrence r...

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