Predictors of prolonged benefit from palbociclib plus fulvestrant in women with endocrine-resistant hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer in PALOMA-3.

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Authors

Cristofanilli, M
DeMichele, A
Giorgetti, C
Turner, NC
Slamon, DJ
Im, S-A
Masuda, N
Verma, S
Loi, S
Colleoni, M
Theall, KP
Huang, X
Liu, Y
Bartlett, CH

Document Type

Journal Article

Date

2018-11-01

Date Accepted

2018-08-16

Date Available

Abstract

BACKGROUND: The addition of palbociclib to fulvestrant improved clinical outcomes over placebo-fulvestrant in endocrine-pretreated metastatic breast cancer (MBC) patients in PALOMA-3. Here, we examined factors predictive of long-term benefit. METHODS: Premenopausal-peri/postmenopausal patients with endocrine-resistant, hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative MBC were randomised 2:1 to fulvestrant (500 mg) and either palbociclib (125 mg/d; 3/1 schedule; n = 347) or placebo (n = 174). Baseline characteristics, mutation status and HR expression levels were compared in patients with and without prolonged benefit (treatment duration ≥18 months). RESULTS: By August 2016, 100 patients (29%) on palbociclib-fulvestrant and 26 (15%) on placebo-fulvestrant demonstrated prolonged benefit, with long-term responders in both arms sharing common clinical characteristics. They usually had less disease burden at baseline versus those treated <18 months, such as having one disease site (40% vs 29% on palbociclib-fulvestrant and 69% vs 29% on placebo-fulvestrant), bone-only disease (32% vs 22% and 46% vs 17%) and were less heavily pretreated (69% vs 56% and 73% vs 60% had ≤2 prior therapies). Baseline tumour ESR1 and PIK3CA mutation rates were lower among long-term responders in both arms; median oestrogen receptor H-scores were similar, whereas progesterone receptor H-scores were higher among long-term responders. CONCLUSIONS: This exploratory analysis demonstrates that some patients with endocrine-resistant MBC derive significant and prolonged benefit when treated with palbociclib-fulvestrant, with fewer patients experiencing similar efficacy with placebo-fulvestrant. The current analysis did not identify specific molecular or clinical factors prognostic of long-term benefit with palbociclib-fulvestrant (ClinicalTrials.gov, NCT01942135).

Citation

European journal of cancer (Oxford, England : 1990), 2018, 104 pp. 21 - 31

Source Title

Publisher

ELSEVIER SCI LTD

ISSN

0959-8049

eISSN

1879-0852

Research Team

Molecular Oncology

Notes