Next Steps Following DESTINY-Breast03 for HER2+ Breast Cancer

Erika P. Hamilton, MD, director of the Breast and Gynecologic Cancer Research Program at the Sarah Cannon Research Institute and medical oncologist at Tennessee Oncology, discusses the next steps following the successful outcomes of the phase 3 DESTINY-Breast03 trial (NCT03529110) of fam-trastuzumab deruxtecan-nxki (Enhertu) in patients with HER2-positive breast cancer.

Based on the primary analysis of the study, trastuzumab deruxtecan showed a 72% reduction in the risk of progression or death versus trastuzumab emtansine (TDM-1) in these patients and adverse events were manageable. These patients must have received a prior trastuzumab (Herceptin)-based regimen, but Hamilton says there are now trials investigating earlier use of trastuzumab deruxtecan in the frontline, adjuvant, and neoadjuvant settings, with the latter 2 showing whether this will be a curative option for patients.

Another area that needs to be investigated is the sequencing of current agents once trastuzumab deruxtecan is used in the second line. Other agents used in HER2-positive disease including capecitabine (Xeloda), tucatinib (Tukysa), and trastuzumab (Herceptin) will need to be investigated in terms of their efficacy following the newer agent and what the optimal sequence is. The role of TDM-1 as a subsequent treatment after trastuzumab deruxtecan will also need to be determined.

TRANSCRIPTION:

0:08 | We are going to continue to bring trastuzumab deruxtecan up into earlier settings, meaning there are ongoing trials in the first-line with trastuzumab deruxtecan as well as both neoadjuvant and adjuvant studies, so studies where patients are in the curative setting. We're excited to see, with how fantastic the results have looked in DESTINY-Breast03, what we might see in earlier lines.

One big remaining question is how do we sequence the drugs we have? If we're conceivably using trastuzumab deruxtecan in the second-line, we have drugs like capecitabine [Xeloda], tucatinib [Tukysa], and trastuzumab that we can use [in the] third-line. We have TDM-1 that we are not…using in the first or second line now. So how do we sequence these and what are the activities of our existing HER2 drugs going to be after patients have already seen trastuzumab deruxtecan? Because we don't have a lot of data on that.