One important message is how you know these data from DESTINY-Breast02 fit into the larger context of T-DXd in HER2-positive metastatic breast cancer, and so I think you have to look at the other study that was presented at San Antonio this year, which was the DESTINY-Breast03 trial, and this was updated data, and DESTINY-Breast03 is comparing T-DXd versus T-DM1 in the second-line setting. So our study, DESTINY-Breast02, looked at post T-DM1...
One important message is how you know these data from DESTINY-Breast02 fit into the larger context of T-DXd in HER2-positive metastatic breast cancer, and so I think you have to look at the other study that was presented at San Antonio this year, which was the DESTINY-Breast03 trial, and this was updated data, and DESTINY-Breast03 is comparing T-DXd versus T-DM1 in the second-line setting. So our study, DESTINY-Breast02, looked at post T-DM1. DESTINY-Breast03, somewhat confusingly because of the numbers, actually looked at the second-line setting, and was a directly head-to-head comparison between T-DXd and T-DM1, and those data, again, we already knew that was a positive trial.
They were updated with longer follow-up here at San Antonio, and those data continue to look very impressive. So now with longer follow-up, the DESTINY-Breast03 trial shows a fourfold improvement in progression-free survival with T-DXd over T-DM1, so a 28-month median PFS compared to about seven months with the T-DM1, so huge difference. Overall-survival in that study is now statistically significant as well. So I think the further updated data from DESTINY-Breast03 in the second-line really are unequivocally, dramatically positive, if you don’t mind me throwing in a couple extra adjectives.
So I think in the clinic, that means we really should be using T-DXd in the second line to take advantage of this really impressive, very long responses, very long disease control in that setting, and the fact that T-DXd also works in later lines is certainly good news, but I think it becomes less clinically relevant over time, because most patients should be getting the drug in the second-line. If you have a patient who has already received T-DM1, and hasn’t received T-DXd yet, then the DESTINY-Breast02 data certainly show that T-DXd is very active in that situation and should be used, but that population is going to get smaller and smaller, and really, T-DXd should be used in the second-line.
