The Evolution of Trastuzumab Deruxtecan in Metastatic Breast Cancer


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Erika P. Hamilton, MD, discusses the evolution of fam-trastuzumab deruxtecan-nxki through its examination in various trials.

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 the evolution of fam-trastuzumab deruxtecan-nxki (Enhertu) through its examination in various trials.

In December 2019, trastuzumab deruxtecan was granted an accelerated approved in by the FDA for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who had received 2 or more prior anti–HER2-based regimens in the metastatic setting. This approval came based on findings from the DESTINY-Breast01 trial (NCT03248492).

According to Hamilton, the DESTINY-Breast03 trial (NCT03529110) examining trastuzumab deruxtecan for patients with HER2-positive unresectable or metastatic breast cancer, took trastuzumab deruxtecan into the second-line space. Further, data from this safety follow-up analysis showed continued benefit and no new safety signals were observed.


0:08 | DESTINY-Breast03 was the trial that really moved trastuzumab deruxtecan into the so-called second-line space. What the safety update aimed to do was to quantify the safety, and also look at some special things like exposure-adjusted incidence rates now that we've had longer follow-up for the patients that were receiving trastuzumab deruxtecan. Essentially at this safety update, our patients that are receiving trastuzumab deruxtecan had now been on treatment for a median of 16 months, so quite a while.

0:43 | What we saw is that grade 3 serious adverse events [AEs] were similar between trastuzumab deruxtecan and T-DM1 at about 53% or 50%, respectively. There were a few more discontinuations of trastuzumab deruxtecan of a little over 14% compared with a little over 7% with T-DM1, but it was largely ILD [interstitial lung disease]/pneumonitis [at] about 8%, that was driving most of those 14% discontinuations for trastuzumab deruxtecan.

1:15 | This special parameter that we looked at, exposure-adjusted incidence rate, is a new one. It's essentially a measure of risk per patient year that is commonly used to describe the safety in long-term studies where the follow-up duration may differ between the 2 arms. When we looked at serious AEs, grade 3 or greater, with all of these with exposure-adjusted incidence rates, they were lower with trastuzumab deruxtecan compared with T-DM1, except 1. The 1 exception was an AE leading to a treatment discontinuation and, again, it was the ILD/pneumonitis that was driving that.

1:54 | Finally, if we looked at the time it took to either get to a point where someone needed to be dose reduced, or the drug was needed to be held, both of those parameters were longer with trastuzumab deruxtecan than they were with T-DM1.

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