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 mutated locally advanced or metastatic HER2- breast cancer. Objective: The aim of the study is to ensure the effectiveness and safety of TALA in real-life 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. Here we present the results of the primary and some secondary endpoints for cohort 1. Results: From November 2018 to May 2021, 86 patients were included in Cohort 1, with updated results after a median follow-up of 17.3 months (11.2 - 24.4). Patients’ characteristics are 53.5% of ER+ BC/46.5% of TNBC (refer to the table). The median Time to Treatment Discontinuation (mTTD) was 9.0 months [range 6.0; 11.5] with 37.7% of patients still on treatment at 12 months. Subgroup analysis shows similar mTTD according HR status, germline vs somatic mutation and prior platinum exposure (refer to the table). The Clinical Benefit Rate assessed by the investigators is 82.4% (Complete Response for 25.7%, Partial response R for 32.4% and stable disease for 24.3%). The median of duration of CNS metastases control was 6.6 months, and 80.0% of patients had control of CNS metastases during TALA. Out of the 85 treated patients, 69 patients (80,2%) experienced a TALA permanent discontinuation for progressive disease (84.1%), toxicity (10.1%), cancer-related death (1.4%), or other reasons (1.4%). After discontinuation of TALA, 65.1% of patients received a subsequent treatment with a TTD of 2.3 months [1.7; 2.7]. The most common subsequent treatments were non-platinum chemotherapy (64.3%), platinum chemotherapy (19.6%) and others (19.1%). At least one adverse events (AEs) was recorded in 74.4% of patients. Hematologic AEs (any grade) occurred in 48.8% (anemia 27.9%, thrombocytopenia 12.8%, neutropenia 10.5%). Most common non-hematologic AEs were alopecia (8.1%) and asthenia (7.0%). Related Serious Hematologic AEs occurred in 10 patients (11.6%) including 7 (8.1%) Anemia. Related Serious Non-hematologic AEs (vomiting, pyelonephritis and ascitis) were seen in 3 patients (3.6%). AEs associated with temporary drug interruption, dose modification and permanent drug discontinuation occurred in 36 (41.9%), 24 (27.9%), and 7 (10.1%) patients respectively. The mOS is expected to be reached at the time of the congress, with 51.9% of patients still alive at 24 months. Conclusions: ViTAL is the largest study that reports real-word data with TALA. Outcomes and safety in Cohort 1 are consistent with the results of EMBRACA study and give additional data on subgroups of interest (ie patients previously treated with carboplatin, presence of CNS). (Litton et al. NEJM 2018) mTTD on subgroups of interest Patients’ characteristics Citation Format: Delphine Loirat, Marie Duboys de la barre, Jean-Christophe Thery, Ioana Hrab, Christelle Jouannaud, Jean-Loup Mouysset, Laura Salabert, Pauline Soibinet, Audrey Mailliez, Romain Valery, Anne Creisson, Cristian Villanueva, Nadine Dohollou, Jean-david Fumet, Thomas grellety, Nathalie Perez-staub, Emma Lachaier, Aurore Iltis-roux, Miguel delbado, Abeer Najem, Romuald Le Scodan, Elsa Curtit, kais aldabbagh, Pascal Pujol, thibault DE LA MOTTE ROUGE. Phase IV study evaluating talazoparib in patients with locally advanced or metastatic negative HER2 breast cancer and a somatic or germline BRCA1/2 mutation (ViTAL) – Analysis of cohort 1 according to hormonal receptor status [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 P4-01-20.