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

Massimo Cristofanilli*, Angela DeMichele, Carla Giorgetti, Nicholas C. Turner, Dennis J. Slamon, Seock Ah Im, Norikazu Masuda, Shailendra Verma, Sherene Loi, Marco Colleoni, Kathy Puyana Theall, Xin Huang, Yuan Liu, Cynthia Huang Bartlett

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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).

Original languageEnglish (US)
Pages (from-to)21-31
Number of pages11
JournalEuropean Journal of Cancer
Volume104
DOIs
StatePublished - Nov 2018

Keywords

  • Advanced breast cancer
  • Fulvestrant
  • HR+/HER2–
  • Long-term response
  • Palbociclib

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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