A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple negative breast cancer - clinical results and biomarker analysis…

By S. Loibl, M. Untch, N. Burchardi, J. Huober, Bruno Sinn, J. Blohmer, E. Grischke, J. Furlanetto, H. Tesch, C. Hanusch and 13 more. Annals of Oncology, 2019

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BACKGROUND Combining immune-checkpoint inhibitors with chemotherapy yielded an increased response rates in patients with metastatic triple-negative breast cancer (TNBC). Therefore, we evaluated the addition of durvalumab to standard neoadjuvant chemotherapy (NACT) in primary TNBC. PATIENTS AND METHODS GeparNuevo is a randomised phase II double-blind placebo-controlled study randomising patients with TNBC to durvalumab or placebo given every 4 weeks in addition to nab-paclitaxel followed by standard EC. In the window-phase durvalumab/placebo alone was given two weeks prior to start of nab-paclitaxel. Randomization was stratified by stromal tumour infiltrating lymphocyte (sTILs). Patients with primary cT1b-cT4a-d disease, centrally confirmed TNBC and sTILs were included. Primary objective was pCR (ypT0 ypN0). RESULTS A total of 174 patients were randomised, 117 participated in the window-phase. Median age was 49.5 years (range 23-76); 47 patients (27%) were younger than 40 years; 113 (65%) had stage ≥IIA disease, 25 (14%) high sTILs, 138 of 158 (87%) were PD-L1-positive. pCR rate with durvalumab was 53.4% (95%CI 42.5%-61.4%) vs placebo 44.2% (95%CI 33.5%-55.3%; unadjusted continuity corrected χ2P=0.287), corresponding to OR=1.45 (95%CI 0.80-2.63, unadjusted Wald P=0.224). Durvalumab effect was seen only in the window cohort (pCR 61.0% vs 41.4%, OR=2.22, 95%CI 1.06-4.64, P=0.035; interaction P=0.048). In both arms, significantly increased pCR (P<0.01) were observed with higher sTILs. There was a trend for increased pCR rates in PD-L1-positive tumours, which was significant for PD-L1-tumour-cell in durvalumab (P=0.045) and for PD-L1-immune cell in placebo arm (P=0.040). The most common immune-related adverse events were thyroid dysfunction any grade in 47%. CONCLUSIONS Our results suggest that the addition of durvalumab to anthracycline/taxane based NACT increases pCR rate particularly in patients treated with durvalumab alone prior to start of chemotherapy. TRIAL REGISTRATION ClinicalTrials.gov number: NCT02685059.

Subfields: Cancer Research, Oncology

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