Trastuzumab deruxtecan in patients with previously treated HER2-low advanced breast cancer and active brain metastases: the DEBBRAH trial

Vaz Batista, Marta; Pérez-García, José Manuel; Cortez, Patricia; Garrigós, Laia; Fernández-Abad, María; Gion, María; Martínez-Bueno, Alejandro; Saavedra, Cristina; Teruel, Iris; Fernández-Ortega, Adela; Servitja Tormo, Sonia; Ruiz-Borrego, Manuel; de la Haba-Rodríguez, Juan; Martrat, Griselda; Pérez-Escuredo, Jhudit; Alcalá-López, Daniel; Sampayo-Cordero, Miguel; Braga, Sofía; Cortés, Javier; Llombart-Cussac, Antonio

doi:http://dx.doi.org/10.1016/j.esmoop.2024.103699

Trastuzumab deruxtecan in patients with previously treated HER2-low advanced breast cancer and active brain metastases: the DEBBRAH trial

Citation

Vaz Batista M, Perez-Garcia JM, Cortez P, Garrigos L, Fernandez-Abad M, Gion M, Martinez-Bueno A, Saavedra C, Teruel I, Fernandez-Ortega A, Servitja S, Ruiz-Borrego M, de la Haba-Rodriguez J, Martrat G, Perez-Escuredo J, Alcala-Lopez D, Sampayo-Cordero M, Braga S, Cortes J, Llombart-Cussac A. Trastuzumab deruxtecan in patients with previously treated HER2-low advanced breast cancer and active brain metastases: the DEBBRAH trial. ESMO Open. 2024;9(9):103699. DOI: 10.1016/j.esmoop.2024.103699

Abstract

Background: Trastuzumab deruxtecan (T-DXd) is approved for human epidermal growth factor receptor 2 (HER2)-positive and HER2-low advanced breast cancer (ABC). T-DXd has shown encouraging intracranial activity in HER2-positive ABC patients with stable or active brain metastases (BMs); however, its efficacy in patients with HER2-low ABC with BMs is not well established yet. Methods: DEBBRAH is a single-arm, five-cohort, phase II study evaluating T-DXd in patients with central nervous system involvement from HER2-positive and HER2-low ABC. Here, we report results from patients with heavily pretreated HER2-low ABC and active BMs, enrolled in cohorts 2 (n = 6, asymptomatic untreated BMs) and 4 (n = 6, progressing BMs after local therapy). Patients received 5.4 mg/kg T-DXd intravenously once every 21 days. The primary endpoint was intracranial objective response rate per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) for both cohorts. Results: Intracranial objective response rate per RANO-BM was 50.0% [3/6 patients; 95% confidence interval (CI) 11.8% to 88.2%] and 33.3% [2/6 patients; 95% CI 4.3% to 77.7%; P = 0.033 (one-sided)] in cohorts 2 and 4, respectively. All responders had partial responses. Median time to intracranial response was 2.3 months (range, 1.5-4.0 months) and median duration of intracranial response was 7.2 months (range, 2.8-16.8 months). Median progression-free survival per RECIST v.1.1. was 5.4 months (95% CI 4.1-10.0 months). Treatment-emergent adverse events occurred in all patients included (16.7% grade 3). Three patients (25.0%) had grade 1 interstitial lung disease/pneumonitis. Conclusions: T-DXd demonstrated promising intracranial activity in pretreated HER2-low ABC patients with active BMs. Further studies are needed to validate these results in larger cohorts. This trial is registered with ClinicalTrials.gov, NCT04420598.