Erika Hamilton, MD, Sarah Cannon Research Institute, Nashville, Tennessee, discusses the updated survival results from DESTINY-Breast03. In the long-term analysis of this multicenter, open-label phase 3 trial, the superiority of trastuzumab deruxtecan (T-DXd) over trastuzumab emtansine (T-DM1) was reinforced by clinically meaningful improvements in overall survival, progression-free survival, and time to progression on second-line therapy.

With results from DESTINY-Breast03 and DESTINY-Breast06 both presented at the 2024 American Society of Clinical Oncology Annual Meeting, Dr Hamilton stated, “I anticipate using trastuzumab deruxtecan earlier, and I anticipate using it among those patients with even lower HER2 expression.”

Transcript:

Hello, I'm Dr Erica Hamilton and I'm the Director of the Breast Cancer Research Program at Sarah Cannon Research Institute in Nashville, Tennessee.

This year at ASCO 2024, we heard overall survival update of DESTINY-Breast03. As we all recall, DESTINY-Breast03 was already previously presented and in fact led to an FDA-approved indication for trastuzumab [deruxtecan] in second-line metastatic HER2-positive breast cancer. At the previous disclosure, we knew that the overall survival was positive, and specifically that trastuzumab outperformed T-DM1. However, the medians had not been reached in either arm.

At ASCO 2024, we were updated with these medians. If you recall, in terms of progression -free survival, T-DM1 gave us about 7.2 months, and trastuzumab deruxtecan gave 29 months, for a hazard ratio of 0.30. We now know in terms of overall survival that trastuzumab deruxtecan provides about a 10-month benefit in overall survival for the second-line for HER2-positive breast cancer. The values were 42.7 months with TDM-1 and 52 .6 months with trastuzumab deruxtecan.

Another advantage of this longer follow-up was we've had longer time to follow patients that remained on trastuzumab deruxtecan for quite some time and see what the cumulative incidence of ILD/pneumonitis was. We now see that total ILD/pneumonitis is about 16.7%. There were a couple additional cases of ILD, all grade 2, none severe, compared to 3.5 % at TDM-1. There's been a lot of talk about ILD preferentially occurring earlier in treatment, perhaps in the first year. And we did see this, about 10% of ILD will occur in the first year. We see about 4.2 percent in year 2 and 2.3 percent of ILD in year 3. Certainly this risk doesn't go away, but very encouraging data that we've really been all but able to eliminate severe cases of ILD and the cases that we do see are grade 1, grade 2, and very infrequently to be grade 3.

We also saw some exciting data from one of the sister studies, DESTINY-Breast06 [DB-06] presented by Dr [Giuseppe] Curigliano [MD, PhD, European Institute of Oncology, Milan, Italy]. This was in a little bit different setting. It was among HER2-low, and what was different from DESTINY-Breast04 was that DB-06 was in HER2-ultralow. Those patients that had an IHC of even 0, but had some membrane staining. The other difference was, trastuzumab deruxtecan was given as first line cytotoxic, not after 1 previous chemotherapy. And this trial was wildly positive.

I anticipate using trastuzumab deruxtecan earlier, and I anticipate using it among those patients with even lower HER2 expression.

Source:

Hamilton EP, Hurvits SA, Im S-A, et al. Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (pts) with HER2+ metastatic breast cancer (mBC): Updated survival results of DESTINY-Breast03. Presented at the 2024 ASCO Annual Meeting. May 31-June 4, 2024; Chicago, IL. Abstract #1025

Curigliano G, Hu X, Dent RA, et al. Trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-low or HER2-ultralow metastatic breast cancer (mBC) with prior endocrine therapy (ET): Primary results from DESTINY-Breast06 (DB-06). Presented at the 2024 ASCO Annual Meeting. May 31-June 4, 2024; Chicago, IL. Abstract #LBA1000