IntroductionThe management of metastatic oestrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) negative advanced breast cancer has evolved with the introduction of CDK4/6 inhibitors improving disease outcomes when added to an AI in the first line setting. The FDA evaluated toxicity of all CDK4/6 inhibitors in women ≥75 years (n=198), and found increased toxicity and dose modifications [1], however, toxicity profiles differ between the CDK4/6 inhibitors. Palbociclib has been shown to be well tolerated in patients ≥75 years (n=83) [2] and ≥ 70 years (n=92) [3], however, more real-world data is essential to inform prescribing practices in larger datasets.MethodsWe undertook a national multi-centre retrospective study with 15 cancer centres participating. All patients aged ≥75 years with ER+/HER2- advanced breast cancer who had received at least 1 cycle of Palbociclib + AI as part of a patient access scheme or NICE approved by 1st December 2019 were included. Data collected included baseline characteristics, comorbidities, disease characteristics, toxicities with palbociclib, dose modifications, dose delays, discontinuation and response to treatment.ResultsData from 123 patients aged ≥75 years are included in this analysis from 3 UK cancer centres. Median age was 79 years (range 75 - 90). 98% had an ECOG performance status of 0-2. Co-morbidities were scored using Charlston comorbidity index (CCI - higher score signifies more co-morbidities). 102 patients had a CCI of ≤10 and 18 had a CCI >10. The starting dose of palbociclib was 125mg in 115 patients, but 8 (6.5%) patients started at a lower dose, a third of whom had a CCI of >10. The average number of concurrent medications was 4 (range 0-12). Visceral metastases were present in 52% of patients, and 33 patients (26.8%) had bone only metastases. The median number of cycles received was 10 (range 1 -36). 60 (48.8%) patients required one dose reduction, 18 patients required a 2nd dose reduction and 2 patients required a 3rd dose reduction. The most common cause for dose reductions was neutropenia G3-4 (n=31) and fatigue G1-3 (n=12). 75 patients (61%) required a dose delay and 9% of patients discontinued treatment due to toxicity. The rate of all grade neutropenia was 88.6% with only 1 patient (0.8%) developing febrile neutropenia. Other all grade common toxicities were fatigue (62.6%), anaemia (61.8%) and thrombocytopaenia (57.7%). 12 (9.7%) patients required hospital admission due to side effects of treatment. At the time of data analysis, 111 patients had had a radiological response assessment and the best response was stable disease in 57.7%, partial response in 32.4% and complete response in 0.9% (1 patient) with a clinical benefit rate (CR+PR+SD ≥24 weeks) of 83.8%. 10 patients (9%) had disease progression. The median progression free survival is immature, but at the time of this analysis was 13 months (range 1-36 months).ConclusionOur real world data contributes to the existing smaller published datasets in the over 75s to reassure clinicians that palbociclib is an effective and manageable treatment choice in older women. Compared to published data in older patients [2, 3], febrile neutropenia rates from palbociclib were lower. Despite a higher dose reduction and delay rate than published data [3], the clinical benefit rate was not adversely affected and the early PFS signal is reassuring.
Citation Format: Salma El Badri, Daniel Hills, Alicja Synowiec, Catherine Harper-Wynne, Maung Moe, Caroline Wilson. Tolerability and efficacy of palbociclib in combination with an aromatase inhibitor (AI) in older women (≥75 years) with ER +ve, HER2-ve metastatic breast cancer. A large ‘real world’ UK multi-centre study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-25.
