Erika P. Hamilton, MD, discusses the purpose of a safety follow-up analysis for the DESTINY-Breast03 trial of fam-trastuzumab deruxtecan-nxki in patients with HER2-positive breast cancer.
Erika P. Hamilton, MD, director of the Breast and Gynecologic Cancer Research Program at the Sarah Cannon Research Institute, discusses the purpose of a safety follow-up analysis for the DESTINY-Breast03 trial (NCT03529110) of fam-trastuzumab deruxtecan-nxki (Enhertu) in patients with HER2-positive breast cancer.
The phase 3 trial randomly assigned patients 1:1 to receive either trastuzumab deruxtecan or trastuzumab emtansine (TDM-1; Kadcyla) intravenously (IV) every 3 weeks. Based on the primary analysis, trastuzumab deruxtecan showed a 72% reduction in the risk of progression or death in these patients. The safety follow-up presented at the 2022 American Society of Clinical Oncology Annual Meeting showed no new safety signals.
Hamilton says trastuzumab deruxtecan appeared to have higher rates of nausea, vomiting, and hair loss, which peaked in the early cycles of treatment. Rates of fatigue were similar in both arms. In general, rates of any-grade adverse events (AEs), grade 3 or higher AEs, and serious AEs were similar across both arms, and were lower with trastuzumab deruxtecan when adjusted for exposure.
She notes that patients in the experimental arm were not required to receive antiemetic supportive care, which may have contributed to higher rates of nausea and vomiting. Now that trastuzumab deruxtecan is associated with these AEs, a multidrug anti-nausea regimen is now recommended when prescribing trastuzumab deruxtecan.
0:08 | The methods of the original study were treating patients randomized in a 1:1 fashion to either receive trastuzumab deruxtecan IV every 3 weeks or T-DM1 IV every 3 weeks. With this updated safety, we were looking at specific parameters that we were interested about: nausea, vomiting, alopecia or hair loss, hematologic or blood count parameters. What we saw was nausea and vomiting, as well as alopecia/hair loss, was more common with trastuzumab deruxtecan. It seemed to peak early in initial cycles and then stay about the same throughout the study, not get worse, etc. And for fatigue, it was very similar between trastuzumab deruxtecan and T-DM1.
0:57 | An important caveat was during DESTINY-Breast03 enrollment, there were no mandatory antiemetics or nausea medicines as part of the protocol. It wasn't until during the study that trastuzumab deruxtecan was recognized as a moderately emetogenic drug. Now a multidrug nausea regimen is recommended from the very beginning and is actually included in the trastuzumab deruxtecan label. We hope that now we are doing an even better job of controlling nausea for the patients that are receiving trastuzumab deruxtecan.