Trastuzumab deruxtecan in HER2+ metastatic breast cancer

Trastuzumab deruxtecan is reaffirmed as the standard of care in the second-line setting for patients with HER2+ metastatic breast cancer in an updated analysis of the results of DESTINY-Breast03 trial, recently published in The Lancet. The study also reinforces the established favorable benefit–risk profile of trastuzumab deruxtecan over trastuzumab emtansine with a longer treatment duration.

Multiple HER2-targeted agents are under investigation in patients with HER2+ metastatic breast cancer; however, only two agents are approved in Europe and the USA for use in the second-line setting, trastuzumab emtansine and trastuzumab deruxtecan, with the first that until recently and for years has been the standard as second-line therapy. The positive results from the interim analysis of progression-free survival in DESTINY-Breast03, an open-label, randomised, multicentre, phase 3 trial, resulted in updated guidance and an epochal change for trastuzumab deruxtecan, substituting trastuzumab emtansine and becoming the preferred second-line therapy; now the second interim analysis has evaluated whether overall survival is improved with trastuzumab deruxtecan versus trastuzumab emtansine with longer study follow-up. The updated results come from 524 patients with HER2+ unresectable or metastatic breast cancer previously treated with trastuzumab and a taxane, randomly assigned to receive trastuzumab deruxtecan or trastuzumab emtansine, both administered by intravenous infusion every 3 weeks, for a median duration of follow-up of 28.4 months and 26.5 months respectively. Median progression-free survival was 28.8 months with trastuzumab deruxtecan and 6.8 months with trastuzumab emtansine, with a number of grade 3 or worse treatment-emergent adverse events similar in both groups. «The benefit of trastuzumab deruxtecan was previously demonstrated on the basis of progression-free survival and is now further confirmed by the overall survival results, which are often considered the gold-standard measure of efficacy», authors says. «The clinically meaningful and statistically significant overall survival benefit of trastuzumab deruxtecan versus trastuzumab emtansine and the longest reported median progression-free survival of trastuzumab deruxtecan observed in this trial support the use of trastuzumab deruxtecan as the standard of care for second-line treatment of patients with HER2+ metastatic breast cancer. Additional studies are underway to determine the efficacy and safety of trastuzumab deruxtecan in patients with HER2+ metastatic breast cancer in the first-line setting and in early-stage disease», authors conclude.