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

被引：14

作者：

Batista, M. Vaz ^{[1
,2
]}

Perez-Garcia, J. M. ^{[2
,3
]}

Cortez, P. ^{[4
]}

Garrigos, L. ^{[3
,5
]}

Fernandez-Abad, M. ^{[6
,7
]}

Gion, M. ^{[6
]}

Martinez-Bueno, A. ^{[5
]}

Saavedra, C. ^{[6
]}

Teruel, I. ^{[8
]}

Fernandez-Ortega, A. ^{[9
]}

Servitja, S. ^{[10
]}

Ruiz-Borrego, M. ^{[11
]}

de la Haba-Rodriguez, J. ^{[12
]}

Martrat, G. ^{[2
]}

Perez-Escuredo, J. ^{[2
]}

Alcala-Lopez, D. ^{[2
]}

Sampayo-Cordero, M. ^{[2
]}

Braga, S. ^{[1
]}

Cortes, J. ^{[2
,3
,13
]}

Llombart-Cussac, A. ^{[2
,14
,15
]}

机构：

[1] Hosp Prof Doutor Fernando Fonseca EPE, Lisbon, Portugal

[2] Med Scientia Innovat Res MEDSIR & Oncoclin & Co, Sao Paulo, Brazil

[3] Int Breast Canc Ctr IBCC, Quiron Grp, Pangaea Oncol, Barcelona, Spain

[4] Hosp Ruber Int, IOB Inst Oncol, Quiron Grp, Madrid, Spain

[5] Hosp Univ Dexeus, Barcelona, Spain

[6] Hosp Ramon & Cajal, Med Oncol Dept, Madrid, Spain

[7] Alcala Henares Univ, Fac Med, Madrid, Spain

[8] Inst Catala Oncol Oncol Badalona ICO, Barcelona, Spain

[9] Inst Catala Oncol Oncol LHosp Hosp ICO, Barcelona, Spain

[10] Hosp Mar, Barcelona, Spain

[11] Hosp Univ Virgen Rocio, Seville, Spain

[12] Univ Cordoba, Hosp Reina Sofia, Inst Maimonides Invest Biomed, Cordoba, Argentina

[13] Univ Europea Madrid, Fac Biomed & Hlth Sci, Dept Med, Madrid, Spain

[14] Hosp Arnau Vilanova, FISABIO, Valencia, Spain

[15] Univ Catolica Valencia, Valencia, Spain

来源：

ESMO OPEN | 2024年 / 9卷 / 09期

关键词：

advanced breast cancer; active brain metastases; HER2-low; T-DXd; trastuzumab deruxtecan; GUIDELINE; EMTANSINE;

D O I：

10.1016/j.esmoop.2024.103699

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 HER2positive ABC patients with stable or active brain metastases (BMs); however, its efficacy fi cacy in patients with HER2-low ABC with BMs is not well established yet. Methods: DEBBRAH is a single-arm, fi ve-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 n = 6, asymptomatic untreated BMs) and 4 (n 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 fi dence 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.

引用

页数：9

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