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

Eur J Cancer. 2018 Nov;104:21-31. doi: 10.1016/j.ejca.2018.08.011. Epub 2018 Oct 8.

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).

Keywords: Advanced breast cancer; Fulvestrant; HR+/HER2–; Long-term response; Palbociclib.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Hormonal / pharmacology
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Carcinoma / chemistry
  • Carcinoma / drug therapy
  • Carcinoma / secondary*
  • Disease-Free Survival
  • Double-Blind Method
  • Drug Resistance, Neoplasm
  • Estrogens*
  • Female
  • Follow-Up Studies
  • Fulvestrant / administration & dosage
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Proteins / analysis
  • Neoplasms, Hormone-Dependent / chemistry
  • Neoplasms, Hormone-Dependent / drug therapy
  • Neoplasms, Hormone-Dependent / secondary*
  • Piperazines / administration & dosage
  • Progesterone*
  • Progression-Free Survival
  • Proportional Hazards Models
  • Pyridines / administration & dosage
  • Receptor, ErbB-2 / analysis
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis

Substances

  • Antineoplastic Agents, Hormonal
  • Estrogens
  • Neoplasm Proteins
  • Piperazines
  • Pyridines
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Fulvestrant
  • Progesterone
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • palbociclib

Associated data

  • ClinicalTrials.gov/NCT01942135