Is there a role for adjuvant pembrolizumab/capecitabine in a patient with TNBC who receives neoadjuvant AC-T with residual disease found at time of surgery?

Based on CREATE-X, there would be data to support using adjuvant capecitabine in this scenario. As for pembrolizumab, there is emerging data that the benefit of the checkpoint inhibitor may be limited to the neoadjuvant setting based on the recent negative IMpassion030 trial of adjuvant atezolizumab reported at SABCS 2023 (NCT03498716). A working hypothesis is that the immune repertoire expands better when the primary breast tumor is in place during checkpoint therapy versus against residual mic...

I would not offer immune checkpoint inhibitor in this setting. The ALEXANDRA/IMpasssion 030 trial of adjuvant atezolizumab, presented at SABCS 2023, was essentially negative. SWOG 1418 has been closed to accrual for a while now, and given that this is an event-driven trial, it makes me speculate that it will not be a positive trial, but this remains to be seen.

I would certainly offer capecitabine in the scenario presented, but not pembrolizumab.

This is an interesting question. Why should NAT with pembrolizumab work to improve pCR and EFS in KN 522, but atezoliuzmab not work as adjuvant therapy in IMpassion030 (as noted below in an SABCS 23 presentation)? Could it be the choice of checkpoint inhibitor? We can only speculate on S1418 (adjuvant pembrolizumab for high risk TNBC) and do await these results. Of note, we also await B59 (NAT with atezolizumab for TNBC). I would agree for NAT use of pembrolizumab, but no post-operative adjuvant...