Impact of CDK4/6 inhibitors on health-related quality of life outcomes in patients with metastatic breast cancer: A systematic review and meta-analysis.

Abstract

The use of cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6is) in treating hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (MBC) have been shown to be effective in prolonging progression-free survival with manageable safety profiles. However, the impact of CDK4/6is on health-related quality of life (HRQoL) is unclear. To comprehensively assess the association of CDK4/6is with HRQoL outcomes in patients with MBC. We searched PubMed, Embase, and ClinicalTrials.gov to identify relevant randomized controlled trials (RCTs) of CDK4/6is on HRQoL outcomes in MBC. The CDK4/6is included in this study were palbociclib, ribociclib, and abemaciclib. Heterogeneity among studies was evaluated via the <i>I</i>² statistic. Of the 18 included RCTs, HRQoL outcomes were most widely measured with the general European Organization for Research and Treatment of Cancer QoL Questionnaire Core 30 (EORTC QLQ-C30) (72%) and the EuroQol-5 Dimension (EQ-5D) (39%). There were no statistically significant differences between CDK4/6is and non-CDK4/6is in the EORTC QLQ-C30 global health status and EQ-5D index scores. Although CDK4/6is were associated with statistically significant worse outcomes in appetite loss, diarrhea, systemic side effects, and upset by hair loss, only the mean difference values for EORTC QLQ-C30 diarrhea of 8.56 (95% CI = 1.05-16.06; <i>P</i> = 0.03; <i>I</i>² = 98%) and EORTC breast cancer-specific upset by hair loss of 10.24 (95% CI = 8.88-11.59; <i>P</i> < 0.00001; <i>I</i>² = 0%) were greater than the published minimum clinically important difference values (EORTC QLQ-C30 diarrhea = 6; EORTC breast cancer-specific upset by hair loss=5). Treatment with CDK4/6is was not generally associated with worsening HRQoL among patients with MBC, except for the symptom-related, patient-reported measures of diarrhea and upset by hair loss. Understanding HRQoL impacts can help support health care decisions and treatment using CDK4/6is for patients with MBC.