Efficacy and safety of adjuvant CDK4/6 inhibitors in hormone receptor-positive, HER2-negative early breast cancer: Updated evidence from a systematic review and meta-analysis.

IntroductionThe long-term survival impact of adding CDK4/6 inhibitors to adjuvant endocrine therapy for hormone receptor-positive, HER2-negative (HR+/HER2-) early breast cancer remains a subject of active evaluation. We performed an updated meta-analysis incorporating the mature efficacy and survival data to comprehensively evaluate the therapeutic benefit and safety profile of adjuvant CDK4/6 inhibitors.MethodsA systematic review and meta-analysis of phase III randomized controlled trials comparing adjuvant CDK4/6 inhibitors plus endocrine therapy with endocrine therapy alone in patients with HR+/HER2- EBC was conducted. The primary outcomes were invasive disease-free survival (IDFS) and overall survival (OS). Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using meta-analytic methods.ResultsFour phase III randomized trials involving 17,784 patients met the inclusion criteria. In the overall analysis, adjuvant CDK4/6 inhibition significantly improved IDFS compared with endocrine therapy alone. In the prespecified analysis restricted to monarchE and NATALEE, adjuvant abemaciclib and ribociclib significantly reduced the risk of invasive disease recurrence (pooled HR 0.69, 95% CI 0.63-0.76; I2 = 0%) and demonstrated a significant overall survival benefit with mature follow-up (pooled HR 0.83, 95% CI 0.73-0.94; I2 = 0%). In contrast, the palbociclib trials (PALLAS and PENELOPE-B) failed to demonstrate improvements in either IDFS or OS. Treatment with CDK4/6 inhibitors was associated with a higher incidence of grade ≥3 adverse events.ConclusionsAbemaciclib and ribociclib significantly improve IDFS and are associated with emerging OS benefits in patients with high-risk HR+/HER2- early high risk breast cancer, whereas palbociclib has not shown comparable efficacy.