Abstract P4-10-03: Potential risk factors for health-related quality of life (HRQoL) in palbociclib (PAL) plus endocrine therapy (ET) and ET alone patients with HR+/HER2- advanced breast cancer (ABC): exploratory analysis from 6-month longitudinal st

Abstract Background: PAL is a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) for the treatment of HR+/HER2- ABC. In phase 3 clinical trials, HRQoL was generally maintained and/or improved in patients (pts) treated with PAL+ET compared with placebo+ET. Previously, we reported that PAL+ET and ET monotherapy did not impact on HRQoL or physical activity (SABCS2023, PO1-05-06). Here, we explored potential risk factors related to HRQoL changes in the pts treated with PAL+ET or ET alone evaluated with a mobile application. Methods: This prospective, observational, multicenter study was conducted in Japanese women with HR+/HER2- ABC initiating PAL+ET (Group 1) or ET alone (Group 2) in 1L/2L setting. HRQoL was assessed using EORTC-QLQ-C30 at baseline and Day 15 of each cycle via a smartphone-based app for 6 cycles (24 weeks). Patient data, including baseline characteristics, treatment, and adverse events, were collected via electronic case report forms. A multivariate mixed effects model was conducted to explore risk factors for HRQoL changes, including treatment group, cycle, baseline HRQoL, line of therapy, education, employment, menopausal status, ECOG-PS, TMN stage, BMI, visceral metastases, and dose reduction as fixed effects. This was exploratory analysis and a trend of GHS change and related risk factors were evaluated. Positive score of estimated mean change represents improvement of global health status (GHS), and negative score represents deterioration of GHS. Results: Ninety-nine pts were enrolled (Group 1: 78, Group 2: 21). Pts had a median age of 56/52 years (Group 1/2); 51%/33% had visceral metastases; 59%/43% were stage IV at initial diagnosis; 36%/33% were fully employed. In each group, 95% (78 pts and 20 pts, respectively) completed the 6-cycle observation period. In the overall population for each group, GHS was maintained across the observation period. Based on the analysis, treatment cycle demonstrated an association with GHS change from baseline score in early cycles (Cycle 2: mean change=4.79, 95%CI 0.93-8.65,; Cycle 3: mean change=6.53, 95%CI 2.75-10.31, p=0.001). Later cycles 4-6 continued to show a trend toward improvement in QOL; however these were less prominent. Additional trends included that CDK4/6i combination treatment (mean change=3.02, 95%CI -4.04- 10.07), first-line treatment (f mean change=2.87, 95%CI -4.18-9.93), and part-time employment (mean change=3.82, 95%CI -3.68- 11.32), which all showed improvement towards GHS from baseline; whereas, stage IV/other (mean change=-2.45, 95%CI -8.58- 3.65) and dose modification (mean change=-2.06, 95%CI -6.02-1.90) trended towards GHS decrease from baseline. Notably, by cycle 4, 91 pts remained on study (Group 1: 73, Group 2: 18). Conclusion: In this Japanese cohort, a gradual improvement in HRQoL was observed in the initial cycles of PAL+ET and ET alone. Although this is a small cohort of pts, our exploratory data provide an initial hypothesis around which pts may experience a benefit/detriment in HRQoL. Further investigation is warranted. (NCT04736576) Citation Format: Shigehira Saji, Mari Oba, Aya Ueda, Kaori Terata, Mihoko Doi, Shigenori Nagai, Masaya Hattori, Kenichi Watanabe, Nobuko Tamura, Manabu Futamura, Kei Koizumi, Naoki Niikura, Tempei Miyaji, Yasuaki Muramatsu, Linghua Xu, Asuka Matsui, Norikazu Masuda, Hiroko Bando. Potential risk factors for health-related quality of life (HRQoL) in palbociclib (PAL) plus endocrine therapy (ET) and ET alone patients with HR+/HER2- advanced breast cancer (ABC): exploratory analysis from 6-month longitudinal study (JBCRG-26) [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 P4-10-03.