Immune checkpoint inhibition in the treatment of early stage triple negative breast cancer: 2021 update()

There is an emerging body of evidence regarding the use of immunotherapy in early-stage triple negative breast cancer (TNBC), with the recent publication of several phase III and randomised phase II studies examining the role of immune checkpoint inhibitors (ICI) in the neoadjuvant setting in combination with chemotherapy. Evidence to date suggests that the addition of PD-1/PD-L1 inhibitors results in slight increases in the rate of pathologic complete response (pCR) seen at the time of surgery, and improved event free survival (EFS) has now been reported. However, a number of questions remain such as the optimal chemotherapy backbone; whether traditional third generation chemotherapy regimens can safely be de-escalated in the presence of an ICI; and the most appropriate sequencing of treatment in order to best harness a durable immune response and if continuation of post operative ICI is needed if one achieves a pCR. A predictive biomarker is also yet to be established, given that PD-L1 protein expression does not seem discriminatory. Given that long-term clinical outcome improvements seen thus far in early stage trials do not seem to be mediated through small changes in pathological complete response rates, new approaches in early stage trial design are now needed.