Efficacy and safety of PARP inhibitors in metastatic breast cancer patients with homologous recombination repair pathway gene mutations: a retrospective multicenter real-world study

Background: The efficacy and safety of poly (ADP-ribose) polymerase inhibitors (PARPis) in the Chinese real-world setting have not been well characterized. Design: This is a retrospective analysis of PARPis efficacy in metastatic breast cancer (MBC) patients with homologous recombination repair (HRR) gene pathogenic variants (PVs). Objectives: We aimed to evaluate the efficacy and toxicities of PARPis in real-world MBC patients. Methods: Patients who received PARPi for MBC at the National Cancer Center and two other centers between January 1, 2019, and December 31, 2024, were consecutively included. The primary endpoint was progression-free survival (PFS). Univariable and multivariable Cox proportional hazard models were used to evaluate the predictive impact of clinicopathologic characteristics on PFS. Results: In total, 62 MBC patients treated with olaparib ( N = 55), talazoparib ( N = 4), pamiparib ( N = 2), and fluzoparib ( N = 1) were enrolled. The median PFS (mPFS) in all patients was 6.0 months (95% confidence interval: 4.1–7.9). mPFS in the germline BRCA1 (g BRCA1; N = 19), g BRCA2 ( N = 30), g BRCA ( N = 4), somatic BRCA2 (s BRCA2; N = 1), g PALB2 ( N = 4), and other HRR gene ( N = 4) PVs carriers were 3.7, 8.0, 2.8, 2.7, 5.3, and 7.1 months, respectively ( p = 0.334). In multivariate analysis, ⩽40 years old (hazard ratio (HR): 2.281, p = 0.008), third-line or later therapy (HR: 2.429, p = 0.019), and prior platinum-based treatment (HR: 2.172, p = 0.014) were independently associated with shorter PFS. The incidence of adverse events (AEs) of all grades was 62.5% (35/56). The most common AEs in all grades were anemia (30.4%), nausea (21.4%), and leukopenia (17.9%). Hematologic toxicity was the most common grade ⩾3 AEs. Conclusion: PARPis showed promising PFS and tolerable toxicity in the real-world treatment of Chinese MBC patients with HRR-related gene mutations.