Sara A. Hurvitz, MD, on Updated Survival Results on T-DXd vs T-DM1 in Metastatic Breast Cancer

DESTINY-Breast 03 was a phase 3 randomized clinical trial looking at T-DXd versus T-DM1 in patients with HER2-positive metastatic breast cancer that had progressed after trastuzumab and a taxane. The primary endpoint was median progression-free survival by blinded independent central review. And a key secondary endpoint was overall survival. The data were originally presented in September 2021 when we showed a stunning significant improvement in median PFS associated with T-DXd, and that was really immediately practiced changing. But the overall survival data were not mature at that time. So at San Antonio we provided updated overall survival results. We had seen 169 overall survival events in July 2022, which triggered the analysis. We showed that the median overall survival had not been reached yet for either treatment arm. However, there was a statistically significant improvement in overall survival seen with T-DXd. The hazard ratio was 0.64. In addition, we presented updated median progression-free survival by independent review. And now the median PFS had been met with T-DXd and was 28.8 months, which was roughly four times longer than seen with T-DM1. In addition, we saw an objective response rate of almost 80% with T-DXd, which was higher than with T-DM1. 21% of patients having a complete response compared to 9.5% with T-DM1. So overall the results show real benefits with T-DXd firmly placing this as the standard of care in regions where it's available after trastuzumab and taxane. In terms of safety, the safety data looked fairly similar to what was previously reported. However, there were more all grade ILD events noted this time with longer treatment duration and longer follow-up. 15% or so of patients treated with T-DXd had ILD compared to about 10% at the time of initial reporting. But all of these additional events were grade one or two. There were no new grade three events and zero grade four or five events. So in summary, I think these data really solidly place T-DXd as the standard of care in the second line setting after trastuzumab and taxane. We have exciting studies ongoing looking at T-DXd in the frontline setting, in the adjuvant setting, so I'm looking forward to seeing more data emerge relating to this very effective regimen.