History of Trastuzumab Deruxtecan in HER2+ mBC Treatment

Sara A. Hurvitz, MD, a medical oncologist, associate professor at the David Geffen School of Medicine at UCLA; medical director of the Jonsson Comprehensive Cancer Center Clinical Research Unit; co-director of the Santa Monica-UCLA Outpatient Oncology Practices; and director of the Breast Cancer Clinical Trials Program at UCLA, discusses how fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) rose to become a standard of care treatment for patients with HER2-positive, metastatic breast cancer.

Transcript:

0:09 | Trastuzumab deruxtecan really hit the scene like in 2019 at [the San Antonio Breast Cancer Symposium] when a single-arm phase 2 trial evaluating T-DXd alone in patients with really heavily pretreated, HER2-positive metastatic breast cancer, who were treated with this agent had an objective response rate of over 60%, and a progression-free survival of over 16 months. We've never seen results with HER2 targeted therapy or any therapy for this type of disease and it led to the accelerated approval of T-DXd.

0:48 | The confirmatory phase 3 clinical trial evaluating T-DXd head-to-head against trastuzumab emtansine [T-DM1; Kadcyla] scene was reported in 2021, at ESMO. And this study was the first randomized phase 3 study looking at T-DXd, and it demonstrated a statistically significant improvement in progression-free survival with T-DXd, compared to T-DM1, as well as improvements in terms of objective response rate, and a trend toward an improvement in overall survival. The overall survival at the time of the reporting was not yet mature. So, at San Antonio in 2022 the data from DESTINY-Breast03 [NCT03529110] were updated with overall survival data.

1:34 | Now at the time of this reporting, the overall survival was statistically significantly better with T-DXd. The median overall survival hadn't been reached yet for either treatment arm, but the overall survival hazard ratio was significantly better with T-DXd, with a hazard ratio of 0.64. Moreover, the median PFS for T-DXd had been met at 28.8 months compared to around 6.8 months for T-DM1 and again the objective response rates and clinical benefit rates are better with T-DXd. So, it really was the homerun in favor of T-DXd in patients who'd received 1 prior line of therapy in the metastatic setting with HER2-positive disease.