In what scenarios would you incorporate platinum for patients with localized TNBC?

In the neoadjuvant setting, I include a platinum - specifically carboplatin - in the chemo regimen in essentially all patients with TNBC. Not only have 3 randomized studies (CALGB 40603, BrighTNess and GeparSixto) demonstrated significantly higher pCR rates with addition of carboplatin, if you look at other multicenter studies that utilized either a non-carbo-containing regimen (weekly paclitaxel followed by AC, such as I-SPY2 and GeparSepto) or a carbo-containing regimen (such as GeparX and KEYNOTE-522), the inclusion of carboplatin increases the pCR rate by at least 20%.

In most patients with stage II-III disease, I add carboplatin to weekly paclitaxel x 12 - preferably weekly at AUC 2, which I believe is better tolerated, though I am also...

@Dr. First Last has thoughtfully presented an evidence based case for incorporating platinum in the management of localized TNBC. However, I believe incorporation of platinum in the management of localized TNBC remains controversial and should be individualized and reserved for patients with the highest risk of relapse, after discussion about additional toxicity and lack of conclusive improvement in long term outcomes.

Several Phase II trials like GeparSixto, CALGB 40603, I-SPY 2, GEICAM/2006-03, UMIN000003355, along with Phase III BrighTNess trial, have all reported consistent improvement in pCR; however, improvement in long term outcomes has been inconclusive or lacking. CALGB 40603 failed to show significant improvement in 3-year event-f...

On the question of identifying biomarkers for response to platinum, neither germline/tumor BRCA status, nor identifiers of BRCANess like HRD assay have been shown to be conclusive.

The BrighTNess and GeparSixto studies reported no significant interactions between BRCA mutation status and treatment group. In fact, the GeparSixto study reported improved response rates in the BRCA wildtype patients.

This is clearly in contrast to metastatic TNBC where BRCA mutation predicted for both greater response and PFS in favor of carboplatin over docetaxel, as seen in the TNT trial.