Top Line: Initial reporting of KEYNOTE-522 revealed a ~15% absolute improvement in pathologic complete response (pCR) rates when pembrolizumab was added to neoadjuvant chemo for triple-negative breast cancer.
The Study: As a reminder, this was a huge phase 3 trial that randomized 1174 women with stage II (75%) or III (25%) TNBC, with 80% in each arm having PD-L1+ disease. Finally, at the fourth planned interim analysis at a median follow-up of 3.25 years, a significant difference has emerged in the co-primary endpoint of event-free survival (EFS). At 3 years, EFS was improved from 77% → 85% with the addition of pembro. Again, an equal benefit was seen for those with and without PD-L1+ disease. What’s more, although this was not a pre-planned analysis, a benefit was seen even among those who didn’t achieve a pCR, presumably due to a decreased disease burden nonetheless. The added toxicities of pembro were mainly low-grade endocrinopathies and skin reactions. Let’s pause to appreciate that this really a landmark study, one that will further cement the addition of pembro for all women receiving systemic therapy for localized TNBC. With that said, there remain a few things to consider. First, women in the pembro arm received adjuvant pembro as well for a total of one year on the drug, and this study has no way to distinguish if the bulk (or all) of the benefit comes in the neoadjuvant phase. More specifically, how do we handle the minority of women who don’t achieve a pCR with the addition of pembro? We already discussed that they still seem to benefit from pembro, but would they benefit from another systemic agent?
TBL: The addition of pembro to neoadjuvant systemic therapy and continuation as adjuvant therapy for localized TNBC significantly improves event-free survival. | Schmid, N Engl J Med 2022