Abstract P1-18-28: Phase IV study evaluating effectiveness and safety of talazoparib in patients with locally advanced or metastatic HER2 negative breast cancer and a BRCA1 or BRCA2 mutation (ViTAL)

Abstract

Background: Talazoparib (TALA) is a highly potent PARP inhibitor that has demonstrated clinical benefit in the phase III EMBRACA trial for patients with germline BRCA1 or BRCA2-mutation and a locally advanced or metastatic HER2 negative (HER2-) breast cancer (BC). Methods: ViTAL is an ambispective, multi-center longitudinal, phase IV study that aims to ensure the effectiveness and safety of TALA in the real-world setting among patients with locally advanced or metastatic HER2- BC, with somatic or germline BRCA mutation (sBRCA or gBRCA). This study includes two cohorts: - Cohort 1: patients treated through the French Early Access Program from November 2018 to September 2019. Inclusion of patients with sBRCA mutation was allowed. - Cohort 2: patients treated according to the European Marketing Approval granted 21/09/2021. The primary endpoint is Time to Treatment Discontinuation (TTD) for TALA defined as Time between the date of first dose of TALA and the date of last dose or death. Results: We present the results of Cohort 1 in which includes 85 patients. Patients’ characteristics are as follows: median age 50 years; 46% triple negative BC and 54% ER+ BC; 47% BRCA1-mutated and 53% BRCA2-mutated; 94% gBRCA and 6% sBRCA; 95% ECOG PS 0 or 1; 31% premenopausal status; 40% de novo metastatic BC (mBC). Visceral, bones and central nervous system metastases were found in 61%, 54% and 11% of patients, respectively. No breast or ovarian cancer in first degree relative was found in 35 patients (41%). The median number of prior cytotoxic regimen was 2, 15% were chemo-naïve for mBC; 35% received prior platinum in the neoadjuvant, adjuvant or metastatic setting. For patients with ER+/HER2- mBC the median number of prior endocrine therapy was 2 and 74% of these patients received a CDK4/6 inhibitor prior to TALA. The median follow-up was 17.4 months [range 15.7-20.5]. Of 85 treated patients, 66 patients (78%) experienced permanent discontinuation of TALA due to progressive disease (88%), toxicity (8%), cancer-related death (3%), or other reasons (1.5%). The median TTD for TALA was 9.0 months [range 6.0-11.0] with 35% of patients still in under treatment at 12 months. At least one adverse event (AEs) was recorded in 71% of patients. Hematologic AEs (any grade) occurred in 44% of patients (anemia for 26%, thrombocytopenia for 9%, neutropenia for 8%). The most common non-hematologic AEs were alopecia (6%) and asthenia (5%). Related serious hematologic AEs occurred in 7 (8%) patients including 6 (7%) with anemia. Related serious non-hematologic AEs (vomiting, pyelonephritis) were seen in 2 patients (2%). AEs associated with temporary drug interruption, dose modification and permanent drug discontinuation occurred in 32 (38%), 16 (19%), and 5 (8%) patients respectively. After discontinuation of TALA, 83% of patients received a subsequent treatment with a TTD of 2.4 months [range 1.7-3.3]. The most common subsequent treatments were non-platinum chemotherapy (64%) and platinum therapy (24%). Conclusions: The TTD of 9 months is consistent with the outcomes and safety results of the EMBRACA study. ViTAL, the first real-word study with TALA confirms its interest in locally advanced or metastatic HER2- BC. Analysis of Cohort 2 will occur when data are mature. (Ref Litton JK, Rugo HR, Ellt J et al. Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation. N Engl J Med. 2018; 379:753-763. Citation Format: Delphine Loirat, Marie Duboys de Labarre, Christine Essner, Ioana Hrab, Jean-Christophe Thery, Christelle Jouannaud, Cristian Villanueva, Perrine Vuagnat, Pauline Soibinet-Oudot, Anne Creisson, Audrey Mailliez, Jean-Loup Mouysset, Laura Salabert, Nadine Dohollou, Jean-David Fumet, Thibault De La Motte Rouge, Jean-Michel Vauthier, Maylis Decrop, Pascal Pujol. Phase IV study evaluating effectiveness and safety of talazoparib in patients with locally advanced or metastatic HER2 negative breast cancer and a BRCA1 or BRCA2 mutation (ViTAL) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-18-28.

Characteristics, Treatment, and Outcomes of Real-World Talazoparib-Treated Patients With Germline BRCA-Mutated Advanced HER2-Negative Breast Cancer

“…This study was the first real-world evaluation conducted in the USA. However, similar studies have been conducted in France, 14 Turkey, 15 and Russia 16 and have been published.…”

“…Findings from the real-world US study were also similar to those reported in the phase IV ViTAL study in France, which included 86 patients with g BRCA m HER2- LA/mBC, as the median TTF of talazoparib for US patients was 8.5 months and the median time to treatment discontinuation, defined as the time between the date of the first dose of talazoparib and the date of last dose or death, for patients in the French study was 8.6 months. 14 No difference was observed according to HR status for either study. However, the median rwPFS and rwORR for talazoparib were more favorable in this real-world US study versus those observed in small real-world studies conducted in Turkey ( n = 47) and Russia ( n = 24).…”

“…Several studies have reported patient characteristics, treatment patterns, and outcomes for talazoparib-treated patients with advanced breast cancer in real-world settings in France, 14 Turkey, 15 and Russia. 16 However, to the authors’ knowledge, there are no published studies to date on talazoparib utilization and outcomes in the real-world US setting.…”

Breast Cancer and Genetic BRCA1/2 Testing in Routine Clinical Practice: Why, When and For Whom?

“…Therapy discontinuation because of adverse events was rare (4.3 %) [41]. The initial results of the phase IV ViTAL trial report a median duration of talazoparib treatment of 9 months as well as a low discontinuation rate due to adverse events (8.0%) [42].…”

“…Therapieabbrüche aufgrund von Nebenwirkungen waren selten (4,3 %)[41]. Erste Ergebnisse der Phase-IV-ViTAL-Studie zeigen eine mediane Behandlungsdauer mit Talazoparib von 9 Monaten und ebenfalls eine geringe Abbruchquote aufgrund von Nebenwirkungen (8,0%)[42].Leitlinien und Empfehlungen zur molekularen Diagnostik und TherapieIn ihren im Jahr 2022 aktualisierten Empfehlungen zur Diagnostik und Therapie früher und fortgeschrittener Mammakarzinome hat die Kommission Mamma der Arbeitsgemeinschaft Gynäkologische Onkologie e. V. (AGO) erneut den höchsten Empfehlungsgrad für die Durchführung einer BRCA1/2-Genuntersuchung erteilt bei: 1. jeder therapeutischen Relevanz (z. B. PARPi) und 2. möglicher erblicher Belastung für ein Mamma-und/oder Ovarialkarzinom entsprechend der Familienanamnese und Eigenanamnese (einschließlich TNBC vor dem 60.…”