Addressing Unmet Needs in HER2 Breast Cancer with Trastuzumab Deruxtecan

Erika P. Hamilton, MD, discusses how researchers are addressing unmet needs for patients with HER2-positive breast cancer.

Erika P. Hamilton, MD, lead investigator and director of the Breast and Gynecologic Cancer Research Program at the Sarah Cannon Research Institute/Tennessee Oncology, discusses how researchers are addressing unmet needs for patients with HER2-positive breast cancer.

Hamilton highlights the use of fam-trastuzumab deruxtecan-nxki (Enhertu) in the second-line setting of this patient population based on results of the DESTINY-Breast03 trial (NCT03529110). The trial compared trastuzumab deruxtecan to trastuzumab emtansine and found that patients on the study drug had a 72% reduction of risk of disease progression over TDM-1 (HR, 0.28; 95% CI, 0.22-0.37; P < .0001). Moreover, there was a 12-month progression-free survival rate of 75.8% for paitnets on trastuzumab deruxtecan caompared with 34.1% for patients on trastuzumab emtansine.

A safety follow-up analysis presented at the 2022 Annual ASCO meeting adverse, showed that no new safety signals were observed for patients with HER2-positive unresectable or metastatic breast cancer. While adverse events (AEs) like nausea, vomiting, and hair loss were more common on trastuzumab deruxtecan, however, serious AEs were common between both treatments.

Hamilton also discusses looking beyond trastuzumab deruxtecan in certain scenarios for patients with HER2 positive metastatic breast cancer.


0:06 | We're going to continue to bring trastuzumab dreuxtecan up into earlier settings, meaning, there are ongoing trials in the first line with trastuzumab dreuxtecan, as well as, in both the neoadjuvant and adjuvant setting. [Also], studies where patients are in the curative setting. And so, we're excited to see with how fantastic the results have looked in DESTINY-Breast03 about what we might see in earlier lines.

0:32 | Then I think 1 big remaining question is, how do we sequence the drugs we have? If we're conceivably using trastuzumab dreuxtecan in the second line, we [then] have drugs like capecetibine, tucatinib, and trastuzumab we can use in the third line. We still have TDM-1 that we're not previously using in the first or second line now. So, how do we sequence these [drugs] and what are the activities of our existing HER2 drugs going to be after patients have already seen trastuzumab dreuxtecan, because we don't have a whole lot of data on that.