Clinical effectiveness and safety of olaparib in BRCA-mutated, HER2-negative metastatic breast cancer in a real-world setting: final analysis of LUCY

Abstract

Purpose: The interim analysis of the phase IIIb LUCY trial demonstrated the clinical effectiveness of olaparib in patients with germline BRCA-mutated (gBRCAm), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC), with median progression-free survival (PFS) of 8.11 months, which was similar to that in the olaparib arm of the phase III OlympiAD trial (7.03 months). This prespecified analysis provides final overall survival (OS) and safety data.

Methods: The open-label, single-arm LUCY trial of olaparib (300 mg, twice daily) enrolled adults with gBRCAm or somatic BRCA-mutated (sBRCAm), HER2-negative mBC. Patients had previously received a taxane or anthracycline for neoadjuvant/adjuvant or metastatic disease and up to two lines of chemotherapy for mBC.

Results: Of 563 patients screened, 256 (gBRCAm, n = 253; sBRCAm, n = 3) were enrolled. In the gBRCAm cohort, median investigator-assessed PFS (primary endpoint) was 8.18 months and median OS was 24.94 months. Olaparib was clinically effective in all prespecified subgroups: hormone receptor status, previous chemotherapy for mBC, previous platinum-based chemotherapy (including by line of therapy), and previous cyclin-dependent kinase 4/6 inhibitor use. The most frequent treatment-emergent adverse events (TEAEs) were nausea (55.3%) and anemia (39.2%). Few patients (6.3%) discontinued olaparib owing to a TEAE. No deaths associated with AEs occurred during the study treatment or 30-day follow-up.

Conclusion: The LUCY patient population reflects a real-world population in line with the licensed indication of olaparib in mBC. These findings support the clinical effectiveness and safety of olaparib in patients with gBRCAm, HER2-negative mBC.

Clinical trial registration: Clinical trials registration number: NCT03286842.

Keywords: Breast cancer; Breast cancer 1 gene product; Breast cancer 2 gene product; Kaplan–Meier survival curves; Olaparib; Overall survival; Progression-free survival.

Fig. 1

Kaplan–Meier estimates for a PFS and b OS in the gBRCAm cohort (N = 252). Vertical gray dashed lines and corresponding percentages represent the estimated event rates at 12, 24, and 30 months after starting olaparib treatment.  BRCA BRCA1 and/or BRCA2; CI confidence interval; gBRCAm germline BRCA-mutated; OS overall survival; PFS progression-free survival.  ^aReasons for censoring (n = 45; 17.9%): progression-free at time of analysis (n = 34; 13.5%), lost to follow-up (n = 1; 0.4%), withdrawn consent (n = 7; 2.8%), terminated study for other reason (n = 3; 1.2%).  ^bReasons for censoring (n = 112; 44.4%): still in survival follow-up (n = 79; 31.3%), terminated study before death (n = 33; 13.1% [lost to follow-up (n = 2; 0.8%), withdrawn consent (n = 28; 11.1%), other reasons (n = 3; 1.2%)])

Fig. 2

Kaplan–Meier estimates for a, b PFS and c, d OS in the gBRCAm cohort by HR status and by previous CT for mBC.  BRCA BRCA1 and/or BRCA2; CI confidence interval; CT chemotherapy; gBRCAm germline BRCA-mutated; HR hormone receptor; mBC metastatic breast cancer; OS overall survival; PFS progression-free survival; TNBC triple-negative breast cancer.  ^aYes: received one or two previous lines of CT for metastatic disease (may have also received CT in the neoadjuvant/adjuvant setting).  ^bNo: no previous CT for advanced/metastatic disease but received in the neoadjuvant/adjuvant setting

Fig. 3

Most frequent TEAEs (occurring in > 10% patients) (full analysis set, N = 255). Data are reported as number of patients (%) with: grade < 3 TEAEs (black bars), grade ≥ 3 TEAEs (grey bars) and any-grade TEAEs (right-hand side of graph). TEAEs were graded according to Common Terminology Criteria for Adverse Events version 4.0 and coded to preferred terms using the Medical Dictionary for Regulatory Activities version 24.0. TEAE, treatment-emergent adverse event