UK multicentre real-world data of the use of cyclin-dependent kinase 4/6 inhibitors in metastatic breast cancer

Gullick, G., Owen, C.N., Watkins, W.J. ORCID: https://orcid.org/0000-0003-3262-6588, Cook, S., Helbrow, J., Reed, H., Squires, R., Park, S., Weir, E., Aquilina, F., Webber, N., Nye, E., Atkinson, C., Blair, C., Halstead, A., Daniels, E., Alves, A., Chew, S., Thomas, W., Spensley, S., Beresford, M., Bowen, R. and Robinson, T. 2024. UK multicentre real-world data of the use of cyclin-dependent kinase 4/6 inhibitors in metastatic breast cancer. ESMO Real World Data and Digital Oncology 5 , 100064. 10.1016/j.esmorw.2024.100064

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Abstract

Background Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) are widely used to treat hormone receptor-positive (HR+)/ human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (MBC). This study aimed to capture the real-world efficacy and tolerability of CDK 4/6is. Patients and methods Data were retrospectively collected from five centres in South West England between April 2017 and November 2022. Results Six hundred and sixty-six patients were included (median age 66 years; interquartile range 23-92 years). Five hundred and forty-four (82.7%) were treated with CDK4/6i as first-line therapy and 122 (18.3%) as second-line therapy. Median follow-up time was 28 months (range 0-76 months). Five hundred and thirty-seven received palbociclib (80.6%), 85 patients received abemaciclib (12.8%) and 44 received ribociclib (6.6%). Palbociclib and ribociclib most frequently caused neutropenia (38.2% and 26.4%, respectively) whilst abemaciclib caused diarrhoea (61.2%). Rates of dose reduction (DR) (between 53.8% and 59.2%) and time to first DR were similar for all agents (2-3 cycles). For first-line therapy, median progression-free survival (PFS) was 31 months (25-35 months) for palbociclib, 16 months [9 months-not reached (NR)] for abemaciclib and 44 months (21-NR) for ribociclib. Median overall survival (OS) was 47 months (41 months-NR) for palbociclib and was not reached for abemaciclib or ribociclib. Low patient numbers precluded analysis of second-line therapy. On multivariate analysis, visceral metastases and Eastern Cooperative Oncology Group performance status were associated with shorter PFS and OS, whilst DR was associated with longer PFS and OS. Conclusion These data demonstrate that CDK4/6is are an effective and safe treatment for metastatic HR+/HER2− breast cancer. Efficacy was in line with trial data and other real-world data. DR was associated with improved PFS and OS, suggesting that trials of CDK4/6is at a lower starting dose are warranted.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
ISSN:	2949-8201
Date of First Compliant Deposit:	28 August 2024
Date of Acceptance:	20 August 2024
Last Modified:	29 Aug 2024 07:54
URI:	https://orca.cardiff.ac.uk/id/eprint/171569

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