Abstract PS2-04: Health related quality of life with first- versus second-line CDK4/6 inhibitor use in advanced breast cancer: results from the phase 3 SONIA trial (BOOG 2017-03)

Abstract Background: Adding cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) to endocrine therapy improves outcome in patients with hormone-receptor positive, HER2-negative advanced breast cancer. The phase 3 SONIA trial randomised 1,050 patients to receive CDK4/6i in first- versus second-line in addition to aromatase-inhibitor in first- and fulvestrant in second-line. No significant difference between the strategies was observed in progression-free survival after two treatment lines (PFS2; HR 0.87; 95% CI 0.74 to 1.03) while first-line CDK4/6i use increased toxicity (74% more grade ≥3 adverse events, most often neutropenia) and costs. We now present the health-related quality of life (HRQoL) outcomes in the first- versus second-line CDK4/6i group. Patients and methods: HRQoL was assessed using the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire (version 4) at baseline, 12, 24, 48 and 72 weeks on both first- and second-line treatment and at SONIA treatment discontinuation. FACT-B total scores along with subscale scores for physical (PWB), social (SWB), emotional (EWB), functional well-being (FWB) and the breast cancer subscale (BCS) were calculated for all completed questionnaires within 60 days after SONIA treatment discontinuation. Missing baseline scores were imputed using the mean baseline score. For missing post-baseline timepoints, multiple imputation was employed separately for each score and arm using the predictors age at randomisation, ECOG performance status, baseline score, progression or a serious adverse event within last 3 months and the timepoint of the questionnaire. Mixed linear regression models with a random intercept were used to compare HRQoL over time between the two arms. Response variables were FACT-B total and individual subscales scores and covariates included treatment arm, time (continuous), and baseline HRQoL. We also tested for an interaction between arm and time. A difference of 7-8 points in FACT-B total score and of 2-3 points in subscales was defined as a clinically meaningful difference. Results: Across arms, questionnaire completion rates were high at baseline (88%), as well as over the different time points during first- (82%) and second-line treatment (73%), and at treatment discontinuation (52%). The average difference in FACT-B total and subscale scores between the two arms was close to zero (i.e. no difference) and we found no evidence of an interaction with time. Over time, the observed mean differences using CDK4/6i in second-line as reference, were -0.49 (95% CI -1.88 to 0.90) for the FACT-B total score, -0.19 (95% CI -0.58 to 0.20) for PWB, 0.40 (95% CI -0.04 to 0.83) for SWB, 0.00 (95% CI -0.34 to 0.35) for EWB, -0.05 (95% CI -0.48 to 0.38) for FWB and -0.36 (95% CI -0.77 to 0.05) for BCS. Conclusions: Health-related quality of life, as measured by the FACT-B total score and all subscales, was comparable between the CDK4/6i-first and CDK4/6i-second group during the two protocol-defined treatment lines in SONIA. These data indicate that adding CDK4/6i in first-line compared to second-line does not result in improved HRQoL, providing further justification for deferring the use of CDK4/6i to second-line treatment. Clinical trial registration: NCT03425838 Citation Format: Noor Wortelboer, Seamus Kent, Hedwig M. Blommestein, Annemiek van Ommen-Nijhof, Vincent van der Noort, Esther van den Pol, Cristina Guerrero Paez, Aart Beeker, Karin Beelen, Lisanne C. Hamming, Joan B. Heijns, Aafke H. Honkoop, Paul C. de Jong, Quirine C. van Rossum-Schornagel, Christa van Schaik-van de Mheen, Jolien Tol, Cathrien S. Tromp-van Driel, Suzan Vrijaldenhoven, A. Elise van Leeuwen-Stok, Gabe S. Sonke, Agnes Jager, Inge R. Konings. Health related quality of life with first- versus second-line CDK4/6 inhibitor use in advanced breast cancer: results from the phase 3 SONIA trial (BOOG 2017-03) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr PS2-04.