Trastuzumab deruxtecan shows promise in HER2-positive metastatic breast cancer

Treatment with trastuzumab deruxtecan (T-DXd) provides sustained antitumour activity and shows a consistent safety profile in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) previously treated with trastuzumab emtansine (T-DM1), as shown by the updated survival results from the phase II DESTINY-Breast01 trial.

In this study, patients with HER2-positive mBC who were resistant or refractory to T-DM1 were administered T-DXd 5.4 mg/kg intravenously every 3 weeks until disease progression, unacceptable adverse events, or withdrawal of consent.

Objective response rate (ORR), as confirmed by an independent central review (ICR), was the primary endpoint, while overall survival (OS), duration of response (DoR), progression-free survival (PFS), and safety were secondary.

In patients receiving T-DXd (n=184), the ORR by ICR was 62.0 percent (95 percent confidence interval [CI], 54.5‒69.0). The median OS was 19.1 months (95 percent CI, 24.6‒36.1) and the median PFS was 19.4 months (95 percent CI, 14.1‒25.0), while DoR was 18.2 months (95 percent CI, 15.0‒not evaluable).

Of the patients, 183 (99.5 percent) experienced treatment-emergent adverse events (TEAEs), and 99 (53.8 percent) had one or more grade ≥3 TEAEs. Adjudicated drug-related lung disease/pneumonitis occurred in 29 patients (15.8 percent), of whom five (2.7 percent) had grade 5.

“[T]his updated analysis of DESTINY-Breast01 provides evidence of sustained antitumour activity with T-DXd in heavily pretreated patients with HER2-positive mBC,” the investigators said. “Further confirmation of the results observed in DESTINY-Breast01 is supported by DESTINY-Breast02.6.”