Quality of life with talazoparib versus physician's choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial

Ann Oncol. 2018 Sep 1;29(9):1939-1947. doi: 10.1093/annonc/mdy257.

Abstract

Background: In the EMBRACA phase III trial, talazoparib (1 mg daily, orally) demonstrated a statistically significant improvement in PFS versus physician's choice of chemotherapy (PCT; capecitabine, eribulin, gemcitabine, or vinorelbine) in patients with HER2-negative advanced breast cancer carrying a germline BRCA1/2 mutation; we evaluated patient-reported outcomes (PROs).

Patients and methods: Patients were randomized 2 : 1 to receive talazoparib or PCT. PROs were assessed at day 1 (baseline), the start of each treatment cycle (every 3 weeks), and at the end of treatment, using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-30) and its breast cancer module, QLQ-BR23. Prespecified exploratory analyses included a longitudinal mixed-effect model comparing treatment arms and a time to definitive clinically meaningful deterioration (TTD) analysis carried out in the global health status/quality of life (GHS/QoL), and all functional and symptom scales from the EORTC QLQ-C30 and -BR23 questionnaires. Between-arm TTD comparisons were made using a stratified log-rank test and a Cox proportional hazards model.

Results: Baseline scores were similar between arms. Statistically significant estimated overall improvement from baseline in GHS/QoL was seen for talazoparib compared with statistically significant deterioration for PCT {3.0 [95% confidence interval (CI) 1.2, 4.8] versus -5.4 [95% CI -8.8, -2.0]; between arms, P < 0.0001}. A statistically significant greater delay was observed in TTD in GHS/QoL, favoring talazoparib over PCT [hazard ratio, 0.38 (95% CI 0.26, 0.55; median, 24.3 versus 6.3 months, respectively; P < 0.0001)]. A statistically significant overall change and a statistically significant delay in TTD, all favoring talazoparib, were also observed in multiple functions and symptoms.

Conclusion: Patients who received talazoparib had significant overall improvements and significant delay in TTD in multiple cancer-related and breast cancer-specific symptoms, functions, and GHS/QoL.

Clinicaltrials.gov: NCT01945775.

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 Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Female
  • Germ-Line Mutation
  • Humans
  • Middle Aged
  • Patient Reported Outcome Measures
  • Phthalazines / administration & dosage
  • Phthalazines / adverse effects*
  • Poly(ADP-ribose) Polymerase Inhibitors / administration & dosage
  • Poly(ADP-ribose) Polymerase Inhibitors / adverse effects*
  • Quality of Life*
  • Time Factors
  • Young Adult

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Phthalazines
  • Poly(ADP-ribose) Polymerase Inhibitors
  • talazoparib

Associated data

  • ClinicalTrials.gov/NCT01945775