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Top Line: Please tell us something other than stem cell transplant is in the pipeline for triple negative breast cancer (TNBC).
The Study: KEYNOTE-522 randomized over 1000 women with stage II (75%) or III (25%) TNBC to neoadjuvant systemic therapy +/- the addition of pembrolizumab. While not required, >80% in each arm were PD-L1(+). Systemic therapy consisted of an initial 4 cycles of carboplatin and paclitaxel followed by 4 cycles of doxorubicin and cyclophosphamide. Pembro (or placebo) was given along with both phases plus up to 9 cycles after surgery. Importantly, capecitabine was not allowed. Adjuvant radiation was allowed as indicated and delivered along with the adjuvant pembro. Adding pembro to neoadjuvant therapy significantly increased the co-primary endpoint of pathologic complete response (pCR) rate by 14% (51 → 65%), with both PD-L1(+) and (-) disease achieving equal absolute benefits. Among those who were (+), the improvement was 55→ 69% compared to 30 → 45% if PD-L1 (-). Ok, so what’s the big deal about pCR? Well, for TNBC, which has poorer outcomes than receptor(+) breast cancer, a pCR is associated with significantly better survival. But there still remains a looming question. While the co-primary endpoint of event-free survival favored the pembro arm, there was insufficient followup to prove a statistical improvement. And what about the 9 extra cycles of adjuvant pembro? Are they a “packaged deal?” And should they be dropped for capecitabine if there isn’t a pCR?
TBL: Adding pembro to neoadjuvant chemo for TNBC dramatically improves pCR rate. | Schmid, N Engl J Med 2020