What chemotherapy backbone will you use with pembrolizumab in the neoadjuvant setting for triple negative breast cancer?

I don't have an answer to this, but just opinions. There are several decisions that we will need to make regarding how to best use immunotherapy, unfortunately without much data to guide us:

1) What chemo backbone to use?

2) Do we really need to continue pembro adjuvantly? If so, in whom? Everyone? Only those with residual disease?

3) How will we incorporate other effective adjuvant therapies (e.g. capecitabine, olaparib) with adjuvant pembro? Do we use both? If so, sequentially or concurrently?

Regarding the chemo backbone question, if one is a purist, one would stick to the way it was done in KEYNOTE-522, and use carboplatin. However, I fear that with this approach, we will be overtreating many women who could be cured with chemotherapy alone...

I would caution the comparison with data from GeparNuevo due to the small number of patients and different drugs and schedules. GeparNuevo used neoadjuvant nab-paclitaxel and q2-week EC and KEYNOTE-522 used paclitaxel/carbo and q3-week AC. We know that based on GeparSepto (large phase 3 study), neoadjvuant nab-paclitaxel was clearly superior to paclitaxel in both pCR rate and iDFS in TNBC. Since nab-paclitaxel is not approved for neoadjuvant treatment, I think if we incorporate Pembro in the neoadjuvant setting, we should use the chemo backbone in KEYNOTE-522 (weekly paclitaxel/carbo-AC). One final note is that conventionally, I use weekly carbo AUC2 with weekly paclitaxel if chemo only without checkpoint inhibitor. However, in KEYNOTE-522,...