ESMO 2025 | ADCs in earlier-line metastatic breast cancer: insights from DESTINY-Breast09 & ASCENT-03

I mean, as we can see that ADCs are really shifting into the first line setting across disease subtypes, which I think is exciting to see. So we had seen data from DESTINY-Breast09 at ASCO, which had demonstrated that the combination of T-DXd and pertuzumab did much better than THP. At ESMO, what we saw were the subgroup analyses. So we saw outcomes, for example, by key subsets. So particularly those patients who had PI3K mutations, patients who had hormone receptor positive disease, and then outcomes based on whether someone presented with de novo disease versus recurrent disease. And in fact, very consistently across these groups, we saw that the benefit of T-DXd clearly outweighed the benefits from THP therapy. And so it really showed there wasn’t a subgroup that was not benefiting and that it was very uniform in the benefits for the combination of T-DXd and pertuzumab. So I think just confirming in essence what we saw from the primary results. In terms of ASCENT-03, that was trying to look to see if we could move sacituzumab govitecan, a directed antibody drug conjugate, from the second line and beyond metastatic triple-negative setting into the first line setting. It was specifically focused on those patients who have PD-L1 negative tumors or are otherwise not eligible to receive immunotherapy. And it randomized patients to sacituzumab or treatment of physician’s choice chemotherapy and found a significant improvement in progression-free survival going from 6.9 to 9.7 months. And so I think seeing this also suggests that we can move sacituzumab into that first line triple-negative setting for patients with breast cancer. And so again, I think very exciting data to see these ADCs moving up in the paradigm for metastatic breast cancer.

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