Impact of Comorbidities on Clinical Outcomes and Quality of Life of Patients With Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative (HR+/HER2-) Advanced Breast Cancer Treated With Palbociclib in the POLARIS Study

Cancer Med. 2026 Apr;15(4):e71788. doi: 10.1002/cam4.71788.

ABSTRACT

BACKGROUND: Comorbidities, common in patients with advanced breast cancer (ABC), may impact survival outcomes and health-related quality of life (HRQoL). Here, we report subgroup analyses on the basis of comorbidities of patients from POLARIS (NCT03280303), a prospective, observational study of patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) ABC who were treated with palbociclib plus endocrine therapy in routine clinical practice in North America.

METHODS: Real-world progression-free survival (rwPFS) and overall survival (OS) were evaluated by line of therapy (1 LOT, ≥ 2 LOT), Charlson Comorbidity Index (CCI) score (0, 1-2, and 3+), and common comorbid disorder categories (cardiovascular, psychiatric, metabolic and nutritional, and blood and lymphatic disorders). HRQoL was assessed using the global health status (GHS)/QoL subscale of the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30.

RESULTS: From January 2017 to October 2019, 1250 patients (median age, 64 years) initiated palbociclib-based therapy. Median rwPFS (95% CI) for patients with CCI scores of 0, 1-2, and 3+ were 20.3 (17.1-24.8), 24.2 (19.4-29.5), and 16.8 (11.2-20.8) months in 1 LOT and 13.7 (6.2-19.7), 13.2 (9.4-17.5), and 14.9 (8.0-21.9) months in ≥ 2 LOT, respectively. Median OS durations (95% CI) were 48.8 (37.3-not estimable [NE]), not reached (43.0-NE), and 34.8 (29.1-44.1) months in 1 LOT and 39.0 (30.6-50.5), 37.9 (26.5-42.6), and 31.6 (20.9-45.2) months in ≥ 2 LOT, respectively. Patients with blood and lymphatic disorders had shorter rwPFS and OS than those with other common comorbidities. GHS/QoL was maintained irrespective of CCI score. Patients with a CCI score of 0 had clinically meaningful and statistically significantly higher mean GHS/QoL scores than patients with a CCI score of 3+ at each assessment.

CONCLUSIONS: Patients with HR+/HER2- ABC receiving palbociclib with higher comorbidity burden, especially blood and lymphatic system disorders, had poorer clinical outcomes. GHS/QoL was preserved regardless of comorbidity burden.

TRIAL REGISTRATION: Clinical trial number: NCT03280303.

PMID:42017805 | DOI:10.1002/cam4.71788