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BACKGROUND
Addition of immune checkpoint inhibitors (CPI) to neoadjuvant chemotherapy (NACT) is a promising strategy in early breast cancer, but the optimal duration of therapy is currently unknown. In the GeparNuevo (NCT02685059) trial, addition of durvalumab to NACT as previously reported led to a moderate increase in pCR rate by absolute 9% (p=0.287).

PATIENTS AND METHODS
Durvalumab or placebo 1.5g/placebo q4 weeks plus nab-paclitaxel 125mg/m weekly for 12 weeks, followed by 4 cycles durvalumab/placebo plus epirubicin/cyclophosphamide (EC) q2 weeks was given to cT1b-cT4a-d TNBC patients. Durvalumab was not continued after surgery. Primary objective was pathological complete response (pCR). Secondary endpoints included invasive disease-free survival (iDFS), distant disease-free survival (DDFS) and overall survival (OS).

RESULTS
174 patients were randomised between June 2016 and October 2017. After a median follow-up of 43.7 months, 34 events had occurred. Despite a non-significant increase in the pCR rate, significant differences were observed for 3-year iDFS, DDFS and OS: iDFS was 85.6% with durvalumab vs 77.2% with placebo (HR 0.48, 95%CI 0.24-0.97, stratified log-rank p=0.036); DDFS 91.7% vs 78.4% (HR 0.31, 95%CI 0.13-0.74, p=0.005); OS 95.2% vs 83.5% (HR 0.24, 95%CI 0.08-0.72, p=0.006). pCR patients had 3-year iDFS of 95.5% with durvalumab and 86.1% without (HR 0.22, 95% CI 0.05-1.06). In non-pCR cohort 3-year iDFS was 76.3% vs 69.7% (HR 0.67, 95% CI 0.29-1.54). Multivariable analysis confirmed durvalumab effect independent of the pCR effect. No new safety signals occurred.

CONCLUSION
Durvalumab added to NACT in TNBC significantly improved survival despite a modest pCR increase and no adjuvant component of durvalumab. Additional studies are needed to clarify the optimal duration and sequence of CPIs in the treatment of early TNBC.