We know that about 15-20% of breast cancers are HER2-positive, and currently the second line standard of care is to utilise trastuzumab deruxtecan or T-DXd, which has really demonstrated an unprecedented progression free survival for patients with metastatic HER2-positive disease where we’ve seen a 29-month PFS in a second line setting. Our current first line standard of care is a taxane plus trastuzumab and pertuzumab, which has yielded a PFS of a little under 19 months, so there’s been a lot of interest in trying to move T-DXd to that upfront setting, knowing that it seems like it would potentially be a better treatment option.
We also know that about a third of patients who start first line treatment for HER2-positive disease can’t move on to get a second line of therapy, either due to death or deterioration in health, so moving our most effective treatments upfront has been a big area of interest.
DESTINY-Breast09 was designed to really address this. It took patients who had previously untreated metastatic HER2-positive breast cancer and randomised them to one of three arms to get T-DXd plus placebo, or T-DXd plus pertuzumab or to get a taxane with trastuzumab and pertuzumab. The study was designed to look at progression free survival, comparing T-DXd and pertuzumab to THP, but also comparing T-DXd alone to THP.
The data we’re presenting here at ASCO is the interim analysis, where there is a stringent criteria set for success that was met for the T-DXd and pertuzumab comparison to THP, but was not met for the comparison of T-DXd alone to THP.
What we found was that, for the combination of T-DXd and pertuzumab, there was a significant improvement in progression-free survival when compared to THP, with an improvement in PFS going from 26.9 months to 40.7 months, with a hazard ratio of 0.56, so a 13.8-month difference between the two arms. In essence it suggests that T-DXd and pertuzumab is almost doubling progression free survival in this upfront setting. I think because of that, it could represent a potential new first line standard of care option for patients with metastatic HER2-positive breast cancer.
