Ian Krop, MD, PhD, Smilow Cancer Hospital, Yale New Haven, CT, shares his key takeaways from the San Antonio Breast Cancer Symposium (SABCS) 2022, including how the data from the Phase III DESTINY-Breast02 (NCT03523585) trial fit into the larger context of trastuzumab deruxtecan (T-DXd) in HER2-posititve metastatic breast cancer. The Phase III DESTINY-Breast03 (NCT03529110), investigating trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with metastatic human epidermal growth factor receptor 2-positive (HER2+) breast cancer in the second-line setting, whereas DESTINY-Breast02 investigated T-DXd in later lines. In the second-line, DESTINY-Breast03 demonstrated a progression-free survival (PFS) four times longer with T-DXd than with T-DM1, a 28-month median PFS versus approximately 7 months, respectively, as well as an improved overall-survival (OS), supporting the use of T-DXd in the second-line setting. However, for patients who have already received T-DM1, as per previous protocol, and have yet to receive T-DXd, the DESTINY-Breast02 trial supports the use of T-DXd. This interview took place at the San Antonio Breast Cancer Symposium (SABCS) 2022 in San Antonio, TX.
These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.
Transcript (edited for clarity)
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.