Trastuzumab Deruxtecan in HER2-Positive Metastatic Breast Cancer Patients with Brain Metastases: A DESTINY-Breast01 Subgroup Analysis

• Published in: Cancer discovery 2022-12, Vol.12 (12), p.2754-2762
• Main Authors: Jerusalem, Guy, Park, Yeon Hee, Yamashita, Toshinari, Hurvitz, Sara A, Modi, Shanu, Andre, Fabrice, Krop, Ian E, Gonzàlez Farré, Xavier, You, Benoit, Saura, Cristina, Kim, Sung-Bae, Osborne, Cynthia R, Murthy, Rashmi K, Gianni, Lorenzo, Takano, Toshimi, Liu, Yali, Cathcart, Jillian, Lee, Caleb, Perrin, Christophe
• Format: Article
• Language: English
• Subjects: Brain Neoplasms; Brain Neoplasms - drug therapy; Brain Neoplasms - secondary; Breast Neoplasms; Breast Neoplasms - pathology; Camptothecin; Camptothecin - therapeutic use; Female; Human health sciences; Humans; Immunoconjugates; Immunoconjugates - therapeutic use; Oncologie; Oncology; Receptor, ErbB-2; Research Briefs; Sciences de la santé humaine; Trastuzumab; Trastuzumab - therapeutic use; trastuzumab deruxtecan
• ISSN: 2159-8274; 2159-8290; 2159-8290
• DOI: 10.1158/2159-8290.CD-22-0837

DESTINY-Breast01 (NCT03248492) evaluated trastuzumab deruxtecan (T-DXd; DS-8201) in patients with heavily pretreated HER2-positive metastatic breast cancer (mBC). We present a subgroup of 24 patients with a history of treated brain metastases (BM), a population with limited treatment options. In patients with BMs, the confirmed objective response rate (cORR) was 58.3% [95% confidence interval (CI), 36.6%-77.9%], and the median progression-free survival (mPFS) was 18.1 months (95% CI, 6.7-18.1 months). In patients without BMs (n = 160), cORR was 61.3% and mPFS was 16.4 months. Eight patients (47.1%) experienced a best overall intracranial response of partial response or complete response. Seven patients (41.2%) had a best percentage change in brain lesion diameter from baseline consistent with stable disease. Two patients (8.3%) with BMs and two (1.3%) without BMs experienced progression in the brain. The safety profile of T-DXd was consistent with previous studies. The durable clinical activity of T-DXd in this population warrants further investigation. Advances in treating HER2-positive metastatic breast cancer have greatly improved patient outcomes, but intracranial progression remains an important risk for which few therapeutic options are currently available. T-DXd demonstrated durable efficacy in patients with stable, treated BMs. This article is highlighted in the In This Issue feature, p. 2711.