Résumé
Background: Talazoparib (TALA) is a highly potent, dual-mechanism PARP inhibitor that has demonstrated clinical benefit in EMBRACA Phase III trial for patients with germline BRCA1/2 (BRCA1/2)-mutated locally advanced or metastatic HER2- breast cancer. Objective: The aim of the study is to ensure the effectiveness and safety of TALA in the real-world setting among patients with locally advanced or metastatic HER2- breast cancer, with somatic or germline BRCA1/2 mutation. Methods: ViTAL is an ambispective, multicentric, longitudinal, phase IV study. It includes two ambispective cohorts: - Cohort 1: patients treated through the French Early Access Program and inclusion of patients with somatic BRCA1/2 mutation was allowed. - Cohort 2: patients treated according to the European Marketing Approval granted in 09/21/2021. The primary endpoint of the study is the Time to Treatment Discontinuation (TTD) which is defined as time between the date of first dose of TALA and the date of last dose or death. Results: From November 2018 to May 2021, 85 patients were included in Cohort 2, Patients’ characteristics are: - a median age of 49.0 years; - 65.8% ER+ BC/34.2% TNBC; - 42.1% mBRCA1/55.3 % mBRCA2/2,6% mBRCA1 and mBRCA2. - 85.7% ECOG PS 0 or 1; - 23.4% de novo mBC. - Visceral, bones and CNS metastases were found in 59.0%, 61.5% and 10.3% of patients respectively. - No breast or ovarian cancer family history at 1st degree was found in 39 patients (50.0%). - 38.5% were chemo-naïve; - 21.8% received prior platinum in (neo)adjuvant or metastatic setting, with a median of prior cytotoxic regimen of 1 - For patients with ER+/HER2- ABC the median number of prior endocrine therapy was 1 and 62.0% of these patients received a CDK4/6 inhibitor prior to TALA. - 8 patients (10.3%) had CNS metastases. Out of the 78 treated patients, 57 patients (73.0%) experienced a TALA permanent discontinuation for Progressive disease (80.7%), toxicity (12.3%), cancer-related death (1.8%), or other reasons (1.8%). The median TTD for TALA is 9.6 months [6.7;10.8] with 34.5% of patients still on treatment at 12 months. After discontinuation of TALA, 59.0% of patients received a subsequent treatment with a TTD of 3.9 months [2.1; 45]. The most common subsequent treatments were non-platinum chemotherapy (67.4%), platinum therapy (6.5%) and other (26.1%). The Clinical Benefit Rate assessed by the investigators is 87.6% (Complete Response for 14.1%, Partial Response for 56.3% and Stable Disease for 17.2%). The median duration of CNS metastases control was 10.2 months, and 25.0% of patients had a control of CNS metastases. At least one adverse events (AEs) was recorded in 67.9% of patients. Hematologic adverse events (AEs) (any grade) occurred in 55.1% (anemia 37.2%, thrombocytopenia 16.7%, neutropenia 15.4%). Most common non-hematologic AEs were Nausea (15.4%) and asthenia (15.4%). Related Serious Hematologic AEs occurred in 6 patients (7.7%) including 3 (3.8%) thrombocytopenia and 3 (3.8%) anemia. Related Serious Non-hematologic AEs (metrorrhagia) were seen in 1 patient (1.3%). AEs associated with temporary drug interruption, dose modification and permanent drug discontinuation occurred in 26 (33.3%), 22 (28.2%), and 7 (12.3%) patients respectively. The mOS is not mature for this analysis. Conclusions: ViTAL is the largest study that reports real-word data with TALA. Outcomes and safety in Cohort 2 (patients treated with TALA according to the European Marketing Approval), are consistent with the results of EMBRACA study and with the Cohort 1. (Litton et al. NEJM 2018) Citation Format: Delphine Loirat, Marie Duboys de la barre, Cristian Villanueva, Audrey Mailliez, Nicolas Isambert, Lionel Moreau, Emmanuelle Jacquet, Dominique Spaëth, Anne Creisson, Christelle Jouannaud, Eric Legouffe, Miguel delbado, Laura Deiana, Pauline Soibinet, Ioana Hrab, Thomas grellety, Nadine Dohollou, Raffaele Longo, Jean-Christophe Thery, Jean-david Fumet, Sellam Zineb, Pascal Pujol, thibault DE LA MOTTE ROUGE. Phase IV multicenter study evaluating RWE and the safety of talazoparib in patients with locally advanced or metastatic negative HER2 breast cancer and a BRCA1/2 mutation (ViTAL) - Cohort 2: patients treated according to the EMA [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-01-04.