Real-world outcomes among HER2-positive metastatic breast cancer patients treated with trastuzumab deruxtecan in the United States

Trastuzumab deruxtecan (T-DXd) was FDA approved in December 2019 for the treatment of patients with HER2 + unresectable or metastatic breast cancer (mBC) who have received ≥ 2 prior anti-HER2-based regimens in the metastatic setting. In DESTINY-Breast01 trial, overall response rate was 62% with median duration of response of 18.2 months in HER2 + unresectable/mBC patients receiving T-DXd.

This was a retrospective observational study using electronic medical records from the ConcertAI US Oncology Dataset. Patients (≥ 18 years) with mBC diagnosis who had received ≥ 1 T-DXd infusion were included. Patients who received any T-DXd infusions as part of a clinical trial were excluded. Patient characteristics and treatment history for mBC prior to initiation of T-DXd were assessed descriptively. Patients were followed for up to 6 months from first T-DXd administration to assess duration of T-DXd treatment using Kaplan-Meier (KM) analysis and physician-documented best real-world overall response rate (complete/partial response) [rwORR] while on T-DXd. Incidence rate of adverse events (AEs) [nausea/vomiting (N/V), fatigue, thrombocytopenia, neutropenia, and interstitial lung disease (ILD)] for up to 12 months while on T-DXd were assessed.

204 patients who received T-DXd between December 2019 and October 2021 were included (mean age 58.8 ± 12.4 years, median follow-up 9.4 months). Prior to T-DXd, most patients (88.7%) received ≥2 anti-HER2 regimens [prior T-DM1 (85.8%), prior trastuzumab + pertuzumab combination (71.6%)]. Most patients (91.7%) initiated T-DXd at a 5.4 mg/kg dose and had a median (IQR) cycle length of 22 (7) days. KM analysis showed that 60.6% (95% CI 53.2-67.3%) of patients remained on T-DXd at 6 months from treatment initiation. Among patients with documented tumor response (N=151), rwORR at 6 months was 66.2%. Overall rates of AEs including ILD were lower in this study [N/V (57.4%), fatigue (53.9%), thrombocytopenia (10.3%), neutropenia (5.4%), and ILD (1.5%)] when compared to HER2+ mBC T-DXd clinical trials and is potentially limited by the retrospective nature of the study and/or limited follow-up.

Treatment response and safety profile for T-DXd in this study was generally similar to data observed in HER2+ BC clinical trials, affirming the clinical benefit of T-DXd among HER2+ mBC patients in real-world practice. Further evaluation of long-term outcomes of T-DXd treatment in HER2+ mBC patients is ongoing.