Health-related quality of life with first- vs second-line CDK4/6 inhibitor use in advanced breast cancer: results from the SONIA trial

Abstract Background The SONIA trial demonstrated that addition of cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) to first-line endocrine therapy (aromatase-inhibitor) was not superior in terms of progression-free survival after two treatment lines (PFS2) compared to addition to second-line (fulvestrant), while first-line use increased toxicity (74% more grade ≥3 adverse events) and costs. Understanding the impact of both treatment strategies on health-related quality of life (HRQoL) is critical to inform patient-centered treatment decisions. Methods HRQoL was assessed using the FACT-B and EQ-5D-5L questionnaires at up to 11 time points over the course of both treatment lines (follow-up) until SONIA treatment discontinuation. FACT-B total and subscale scores—including physical (PWB), social (SWB), emotional (EWB), functional well-being (FWB) and the breast cancer subscale (BCS) – along with EQ-5D-5L scores were compared between treatment strategies using mixed linear regression models. Clinically meaningful differences were predefined as 7 points for the FACT-B total score and 2 points for subscales. Results Questionnaire completion rates for FACT-B were 88% at baseline and 75% during follow-up. No clinically or statistically significant differences in HRQoL were observed between treatment arms during follow-up. The estimated mean difference in FACT-B total score (CDK4/6i in second-line as reference) was -0.66 (95% CI -2.14 to 0.82; p = .39). Differences for subscales were similarly small. Conclusion HRQoL was comparable between patients receiving CDK4/6i in first- versus second-line across all measures, despite differences in toxicity rates. Clinical Trial Registration ClinicalTrials.gov (NCT03425838)