Therapy of BRCA-associated metastatic breast cancer. Efficacy and safety of talazoparib in the real-world clinical practice

Introduction. PARP inhibitors demonstrated high efficacy in BRCA1/2-associated Her2-negative metastatic breast cancer (BC). They were included in the current standard chemotherapy regimen and recognized as a priority option for the treatment of such tumours following the results of clinical studies.Aim. Review the experience with talazoparib (Talzenna) in the real-world clinical practice of 6 medical centers in Russia.Materials and methods. The review included data from 29 patients with HER2-negative metastatic breast cancer associated with a gBRCA mutation, who have been receiving talazoparib therapy in 6 medical centers of Russia since April 2021. Talazoparib was given at the standard dose 1 mg once daily, the dose was reduced, if any adverse event developed.Results. The median age of the patients was 50 years. 23 patients had a BRCA1 mutation, 5 patients had a BRCA2 mutation and one of the patients had a PALB2 mutation. Prior to starting talazoparib therapy, patients had received up to 9 lines of therapy for metastatic disease, the median was 1 line. The median follow-up period at that time was only 4.6 months. The median recurrence-free survival (RFS) was not reached. Progression was observed in 10 patients with a treatment period of 1 to 7.5 months, 19 patients continued to receive PARP inhibitor therapy without signs of disease progression, with a treatment period of 2 to 18 months. The objective response rate (ORR) was 57.2%, the clinical efficacy was confirmed in 85.7% of cases. The subgroup analysis showed that the lowest efficacy of therapy was reported in the group of patients, who had received prior therapy with platinum-based drugs, the median progression-free time (mPFT) was 4.5 months. (95% CI: 1.79-9.2). While for patients who had not received the prior platinum drug regimens, the median was not reached. Haematologic toxicities were common adverse events (AEs) for the talazoparib therapy, which were reported in 34.5% of cases. Transfusions of blood components were required in 3 patients, one of them required them repeatedly. All dose modifications were due to hematological toxicities. 7 patients (24.1%) required a dose reduction and 3 patients (10.3%) - repeated dose reduction.Conclusions. Testing for BRCA1/2 mutations in Her2-negative mBC should be a mandatory diagnostic procedure. Talazoparib therapy is an effective and safe treatment option for patients with gBRCAmut HER2-mBC.