Scientific publications

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

Jul 1, 2021 | Magazine: European Journal of Cancer

Karen A Gelmon  1 , Peter A Fasching  2 , Fergus J Couch  3 , Judith Balmaña  4 , Suzette Delaloge  5 , Intidhar Labidi-Galy  6 , James Bennett  7 , Susan McCutcheon  7 , Graham Walker  7 , Joyce O'Shaughnessy  8 , Collaborating Investigators

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.

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