Optimal duration of prior endocrine therapy predicts the efficacy of Fulvestrant in a real-world study for patients with hormone receptor-positive and HER2-negative advanced breast cancer

Cancer Med. 2020 Dec;9(23):8821-8831. doi: 10.1002/cam4.3491. Epub 2020 Oct 6.

Abstract

Fulvestrant 500 mg is standard of care for endocrine therapy-naive or pretreated women with hormone receptor-positive (HR+) metastatic breast cancer (MBC). This study was conducted to explore the potential factors and duration of last endocrine therapy as predictors for the efficacy of fulvestrant 500 mg on Chinese patients in real-world practice. Two hundred and fifty-two MBC patients who were treated with fulvestrant 500 mg consecutively between January 2011 and December 2015 in our institute were included in this study. Efficacy outcomes included progression-free survival (PFS), overall survival (OS), and clinical benefit rate (CBR). The optimal cut-off value for duration of last endocrine therapy was determined by survival ROC analysis. Adverse events were graded according to NCI-CTC AE 4.0. Fulvestrant 500 mg demonstrated a median PFS of 5.8 months (95%CI 4.6-6.9), and a median OS of 35.9 months (95%CI 30.2-41.4). CBR was 41.3% (95%CI 35-47). Liver metastasis, bone alone metastasis, lines of endocrine therapy for MBC, and sensitivity to last endocrine therapy were statistically significant in the Cox multivariate analysis (P values of 0.022, 0.02, 0.03, and 0.038, respectively). The optimal cut-off values for duration of last endocrine therapy to predict the efficacy of fulvestrant 500 mg were 25.08 months for adjuvant endocrine therapy and 5.17 months for first-line endocrine therapy, which showed no difference in prediction power with ABC clinical definition. Patients with prior adjuvant endocrine therapy ≥25.08 months or first-line therapy≥5.17 months reached a longer PFS of fulvestrant (p = 0.04). Six patients discontinued the treatment due to intolerable adverse events. Patients with the duration of prior endocrine therapy longer than optimal cut-off points indicate better PFS of fulvestrant. Liver metastasis, bone alone metastasis, line of fulvestrant, and sensitivity to last endocrine therapy were also predictors for response of fulvestrant. ClinicalTrials.gov Identifier: NCT03708432.

Keywords: fulvestrant; hormone receptor-positive; metastatic breast cancer; real-world effectiveness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Hormonal / adverse effects
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Bone Neoplasms / secondary
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • China
  • Disease Progression
  • Duration of Therapy
  • Estrogen Receptor Antagonists / adverse effects
  • Estrogen Receptor Antagonists / therapeutic use*
  • Female
  • Fulvestrant / adverse effects
  • Fulvestrant / therapeutic use*
  • Humans
  • Liver Neoplasms / secondary
  • Middle Aged
  • Progression-Free Survival
  • Receptor, ErbB-2 / analysis*
  • Receptors, Estrogen / analysis*
  • Receptors, Progesterone / analysis*
  • Retrospective Studies
  • Time Factors

Substances

  • Antineoplastic Agents, Hormonal
  • Estrogen Receptor Antagonists
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Fulvestrant
  • ERBB2 protein, human
  • Receptor, ErbB-2

Associated data

  • ClinicalTrials.gov/NCT03708432