Clinical effectiveness of olaparib monotherapy in germline BRCA-mutated, HER2-negative metastatic breast cancer in a real-world setting: phase IIIb LUCY interim analysis

Eur J Cancer. 2021 Jul;152:68-77. doi: 10.1016/j.ejca.2021.03.029. Epub 2021 Jun 1.


Background: In the phase III OlympiAD trial, olaparib significantly increased progression-free survival (PFS) compared with chemotherapy of physician's choice in patients with germline BRCA-mutated (gBRCAm), human epidermal growth factor 2 (HER2)-negative metastatic breast cancer (mBC). The phase IIIb LUCY trial assessed the clinical effectiveness of olaparib in similar patients, in a setting reflecting clinical practice.

Methods: This open-label, single-arm trial of olaparib (300 mg, twice daily) enrolled patients with BRCAm, HER2-negative mBC who had received taxane and/or anthracycline in the (neo)adjuvant/metastatic setting and not more than two lines of prior chemotherapy for mBC. Patients with hormone receptor-positive mBC had progressed on at least one line of endocrine therapy in an adjuvant/metastatic setting and were unsuitable for further endocrine treatment. This interim analysis was planned after 160 PFS events.

Results: Of 563 patients screened, 252 patients with gBRCAm were enrolled and received at least one dose of olaparib. The median investigator-assessed PFS was 8.11 months (95% confidence interval [CI], 6.93-8.67; 166/252 events [65.9% maturity]). The investigator-assessed clinical response rate was 48.6%, and median time to first subsequent treatment or death was 9.66 months (95% CI, 8.67-11.14). The most common treatment-emergent adverse events (TEAEs; >20% patients) were nausea, anaemia, asthenia, vomiting and fatigue. Eleven patients (4.4%) discontinued treatment because of a TEAE. Grade 3 or higher TEAEs occurred in 64 patients (25.4%), including anaemia (33 patients; 13.1%).

Conclusion: Olaparib was clinically effective in patients with gBRCAm, HER2-negative mBC with safety outcomes consistent with previous findings. identifier: NCT03286842.

Keywords: BRCA1 gene; BRCA2 gene; Breast cancer; Effectiveness; Germline mutation; Metastatic; Olaparib; Progression-free survival; Treatment outcome.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Breast Neoplasms / genetics
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Chemotherapy, Adjuvant / methods
  • Female
  • Germ-Line Mutation
  • Humans
  • Middle Aged
  • Phthalazines / therapeutic use*
  • Piperazines / therapeutic use*
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use*
  • Progression-Free Survival
  • Receptor, ErbB-2 / genetics
  • Young Adult


  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Phthalazines
  • Piperazines
  • Poly(ADP-ribose) Polymerase Inhibitors
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • olaparib

Associated data