Aditya Bardia, MD, on Destiny-Breast06: An Additional Analysis

DESTINY-Breast06 was a pivotal phase III trial that looked at T-DXd or trastuzumab deruxtecan, a HER2-directed ADC versus chemotherapy of physician's choice for patients with metastatic hormone-receptor positive HER2-low, as well as ultra-low metastatic breast cancer. The trial was different from previous studies in that it included patients who had not received prior chemotherapy, so it was in the chemotherapy-naive setting, and it also included patients who had rapid disease progression on first-line therapy with the CDK4/6 inhibitor. So if a patient had disease progression within first six months of first-line therapy, as the next line, they were eligible for this clinical trial. At ASCO 2024, we saw the primary results where patients who received T-DXd had superior progression-free survival as compared to standard chemotherapy. The median PFS was about 13 months with T-DXd, versus eight months with standard chemo. At SABCS 2024, we saw additional results by the pace of disease progression. We saw PFS-II results, and we also saw results based on the amount of disease or disease burden. So if you look at the pace of disease progression, let's start with patients who had rapid disease progression. In that setting, where T-DXd was used just after the first-line therapy, the median PFS was 14 months with T-DXd, versus about six months with standard chemotherapy. This corresponded to a hazard ratio of .38. So clear benefit with T-DXd in that setting. But it also worked in other patients who had longer duration on their CDK4/6 inhibitors, six to 12 or more than 12 as well. If you look at PFS-II, so that is looking at date of randomization till the second disease progression, that was also higher with T-DXd, 20 months, so that's close to two years, versus about 14 months with standard chemotherapy. So the benefit was maintained in the PFS-II setting as well. And then finally, we looked at the amount of disease burden, patients who had less than three metastatic sites versus more than three metastatic sites. Again, the benefit of T-DXd was maintained. We looked at patients who had liver meds versus no liver meds, the benefit of T-DXd was maintained. So overall T-DXd is superior to standard chemotherapy, which included taxanes or capecitabine in this clinical trial, with a median PFS of more than 13 months versus about eight months with standard chemo. So it's a potential option in this setting for patients with both HER2-low as well as ultra-low metastatic breast cancer.