I spy a popular surrogate.

Much the same, everyone knows that pathologic response to neoadjuvant systemic therapy for breast cancer portends a great prognosis. Does this hold true for investigational therapies like immune checkpoint inhibitors as used in I-SPY 2? In a word, yep. In this large prospective trial, 950 women with breast tumors >2.5 cm with high-risk receptor status and/or high-risk genomic scores were randomly assigned to one of nine investigational neoadjuvant treatments. Of these enrollees, just over one-third (n=330) achieved a pathologic complete response (pCR) at time of surgery. As expected, rates were lowest for ER+/HER2- (17%) and highest for ER-/HER2+ (68%). This substudy specifically investigates association of pCR with more clinically meaningful outcomes to determine if this will remain a quick but worthy endpoint for further iterations of the study. Indeed, pCR was associated with an 80% relative reduction in risk of recurrence (HR 0.19) and distant mets (HR 0.21) at 3 years. TBL: Even after investigational therapies like ICI, a pCR portends excellent overall prognosis for all types of breast cancer. | I-SPY2 Trial Consortium, JAMA Oncol 2020