Trastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases: a phase 3b/4 trial

This phase 3b/4 DESTINY-Breast12 study investigated trastuzumab deruxtecan (T-DXd) in patients with HER2+ metastatic breast cancer (mBC), with (n=263) and without (n=241) brain metastases (BMs). Patients received T-DXd (5.4 mg/kg). Primary endpoints were progression-free survival (PFS; BMs cohort) and objective response rate (ORR; non-BMs cohort). In the BMs cohort, 12-month PFS was 61.6%, and 12-month CNS PFS was 58.9%. In the non-BMs cohort, ORR was 62.7%. Grade 3 or higher adverse events occurred in ~50% of patients. These data show substantial and durable overall and intracranial activity for T-DXd, supporting its use in previously treated HER2+ mBC patients regardless of BMs status.

Nadia Harbeck, Eva Ciruelos, Guy Jerusalem, Volkmar Müller, Naoki Niikura, Giuseppe Viale, Rupert Bartsch, Christian Kurzeder, Michaela J. Higgins, Roisin M. Connolly, Sally Baron-Hay, María Gión, Valentina Guarneri, Giampaolo Bianchini, Hans Wildiers, Santiago Escrivá-de-Romaní, Manoj Prahladan, Helen Bridge, Nataliya Kuptsova-Clarkson, Nana Scotto, Sunil Verma, Nancy U. Lin, the DESTINY-Breast12 study group