Palbociclib combined with aromatase inhibitors (AIs) in women >= 75 years with oestrogen receptor positive (ER plus ve), human epidermal growth factor receptor 2 negative (HER2-ve) advanced breast cancer: A real-world multicentre UK study

Abstract

Background Breast cancer accounts for 21% of all cancer diagnoses in women aged ?75 years. The older population is under-represented in clinical trials; thus, real-world data in this patient group is critical to guide management. In this large-scale UK-wide real-world study, we evaluated the tolerability and efficacy of palbociclib combined with an AI for first-line treatment of advanced ER+ve/HER2-ve breast cancer in elderly women. Methods 14 cancer centres participated in this national retrospective study. Patients aged ?75 years who received at least one cycle of palbociclib combined with an AI for first-line treatment of advanced ER+ve/HER2-ve breast cancer were eligible. Data included baseline demographics, co-morbidities, metastatic disease burden, toxicities, dose reductions and delays, response to treatment and in-patient secondary care burden. Multivariable Cox regression was used to assess independent predictors of progression-free survival (PFS). Results 276 patients met the eligibility criteria. The median age of patients was 78 (range 75-92) years. The PFS rates at 12 and 24 months were 75.9% and 64.9%, respectively. The best radiological response was complete response (2%), partial response (32.9%) and stable disease (54.9%) with a clinical benefit rate at 24 weeks of 87%. The most common toxicities were neutropenia, fatigue, anaemia and thrombocytopenia. 50.7% of patients required a dose reduction and 59.2% required at least one dose delay. 22 patients (9.6%) required hospital admission due to toxicity and 6 patients (2.2%) had febrile neutropenia. Multivariable analysis identified fewer dose delays, increasing ECOG performance status and age-adjusted Charlson co-morbidity index, and increasing number of metastatic sites to be independent adverse predictors of PFS. Conclusions This largest known dataset of Palbociclib tolerability and efficacy in women aged ?75 years shows that this is an effective therapy that is well tolerated and appropriately managed with dose delays/reductions resulting in very low levels of clinically significant toxicity requiring hospital admission.