Neoadjuvant durvalumab improves survival in early triple-negative breast cancer independent of pathological complete response

Journal Paper/Review - Aug 9, 2022


Loibl S, Staib P, Link T, Rhiem K, Solbach C, Fasching P, Nekljudova V, Denkert C, Untch M, Jackisch C, Thomalla J, Schneeweiss A, Huober J, Braun M, Rey J, Blohmer J, Furlanetto J, Zahm D, Hanusch C, GBG and AGO-B. Neoadjuvant durvalumab improves survival in early triple-negative breast cancer independent of pathological complete response. Ann Oncol 2022
Journal Paper/Review (English)
Ann Oncol 2022
Publication Date
Aug 9, 2022
Issn Electronic
Brief description/objective

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).

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).

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.

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.