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

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.

Trastuzumab deruxtecan versus treatment of physician's choice in previously treated Asian patients with HER2-low unresectable/metastatic breast cancer: subgroup analysis of the DESTINY-Breast04 study.

BACKGROUND: In the global phase 3 DESTINY-Breast04 study (NCT03734029), the anti-human epidermal growth factor 2 (HER2) antibody-drug conjugate trastuzumab deruxtecan (T-DXd) demonstrated a statistically significant improvement in progression-free survival (PFS) and overall survival (OS), with manageable safety compared with treatment of physician's choice (TPC) in patients with HER2-low metastatic breast cancer (mBC) who had received 1-2 prior lines of chemotherapy. METHODS: This subgroup analysis examined the efficacy and safety of T-DXd versus TPC in 213 patients from Asian countries and regions who were enrolled in the DESTINY-Breast04 trial and randomized to T-DXd (n = 147) or TPC (n = 66). RESULTS: Median PFS with T-DXd and TPC was 10.9 and 5.3 months, respectively, in Asian patients with hormone receptor-positive mBC, and 10.9 and 4.6 months, respectively, in the overall Asian population. In both populations, median OS was not reached with T-DXd and was 19.9 months with TPC. The objective response rate was higher with T-DXd versus TPC in all Asian patients. Median treatment duration was 8.4 months with T-DXd and 3.5 months with TPC. The most common grade ≥ 3 drug-related treatment-emergent adverse events in Asian patients treated with T-DXd were neutropenia (16.3%), anemia (12.9%), and leukopenia (11.6%); the incidences of neutropenia and leukopenia were higher with TPC versus T-DXd. Adjudicated drug-related interstitial lung disease or pneumonitis with T-DXd was 14.3%; the majority of events were grade 1-2. CONCLUSIONS: T-DXd demonstrated clinically meaningful survival benefits versus TPC in Asian HER2-low mBC patients, regardless of hormone receptor status, with no new safety signals. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT03734029.