Palbociclib in combination with aromatase inhibitors in patients ≥ 75 years with oestrogen receptor-positive, human epidermal growth factor receptor 2 negative advanced breast cancer: A real-world multicentre UK study

S El Badri ,Bilal Tahir,Karen Desouza,Alicja Synowiec,Anshu Wadhawan,Richard Simcock,Maung Moe,Anna Stansfeld,Mark Verrill,Yatri Shah,Pavel Bezecny,Thomas Pigott,Fiona Britton,Caroline Wilson,Simon Dixon,Andrew Proctor,David Mark Davies ,Catherine Harper‐Wynne ,M Theodoulou ,D Hills ,K Balachandran

doi:10.1016/j.breast.2021.10.010

Abstract

BackgroundBreast cancer incidence increases with age and real-world data is essential to guide prescribing practices in the older population. The aim of this study was to collect large scale real-world data on tolerability and efficacy of palbociclib + AI in the first line treatment of ER+/HER2-advanced breast cancer in those aged ≥75 years. Methods14 cancer centres participated in this national UK retrospective study. Patients aged ≥75 years treated with palbociclib + AI in the first line setting were identified. Data included baseline demographics, disease characteristics, toxicities, dose reductions and delays, treatment response and survival data. Multivariable Cox regression was used to assess independent predictors of PFS, OS and toxicities. Results276 patients met the eligibility criteria. The incidence of febrile neutropenia was low (2.2%). The clinical benefit rate was 87%. 50.7% of patients had dose reductions and 59.3% had dose delays. The 12- and 24- month PFS rates were 75.9% and 64.9%, respectively. The 12- and 24- month OS rates were 85.1% and 74.0%, respectively. Multivariable analysis identified PS, Age-adjusted Charlson Comorbidity Index (ACCI) and number of metastatic sites to be independent predictors of PFS. Dose reductions and delays were not associated with adverse survival outcomes. Baseline ACCI was an independent predictor of development and severity of neutropenia. ConclusionPalbociclib is an effective therapy in the real-world older population and is well-tolerated with low levels of clinically significant toxicities. The use of geriatric and frailty assessments can help guide decision making in these patients.

Highlights

Breast cancer incidence increases with age and real-world data is essential to guide prescribing practices in the older population
The introduction of cyclin-dependent kinase (CDK) 4/6 inhibitors into routine clinical practice has changed the paradigm of management of oestrogen receptor-positive (ERþ), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer
Three CDK4/6 inhibitors are currently approved in the UK and are being used in clinical practice in first line with an aromatase inhibitor (AI) and second line with fulvestrant: palbociclib, abemaciclib and ribociclib

Summary

Introduction

Breast cancer incidence increases with age and real-world data is essential to guide prescribing practices in the older population. With the older population representing a growing proportion of these patients, it is important to carefully evaluate the available evidence in this group, considering they are underrepresented in clinical trials Those older patients included in trials tend to be highly selected with a lower risk profile compared to the real-world population, with that disparity increasing with increasing age [2,3]. Three CDK4/6 inhibitors are currently approved in the UK and are being used in clinical practice in first line with an aromatase inhibitor (AI) and second line with fulvestrant: palbociclib, abemaciclib and ribociclib These agents have some overlapping toxicities, specific side effects are unique to, or more frequently encountered with, certain agents. Given that palbociclib was the first agent to be approved and is one of the most frequently prescribed drugs in its class in the UK, it was selected as the agent of choice for this study

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