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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 of GeparNuevo study

Loibl S, Untch M, Burchardi N, Huober J, Sinn BV, Blohmer JU, Grischke EM, Furlanetto J, Tesch H, Hanusch C, Engels K, Rezai M, Jackisch C, Schmitt WD, Von Minckwitz G, Thomalla J, Kümmel S, Rautenberg B, Fasching P, Weber K, Rhiem K, Denkert C, Schneeweiss A (2019)

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Publication Type: Journal article

Publication year: 2019

Journal

Book Volume: 30

Pages Range: 1279-1288

Journal Issue: 8

DOI: 10.1093/annonc/mdz158

Abstract

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 2 weeks before start of nab-paclitaxel. Randomisation 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 pathological complete response (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% to 61.4%) versus placebo 44.2% (95% CI 33.5% to 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% versus 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 before start of chemotherapy. Trial registration: ClinicalTrials.gov number: NCT02685059.

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APA:

Loibl, S., Untch, M., Burchardi, N., Huober, J., Sinn, B.V., Blohmer, J.U.,... Schneeweiss, A. (2019). 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 of GeparNuevo study. Annals of Oncology, 30(8), 1279-1288. https://doi.org/10.1093/annonc/mdz158

MLA:

Loibl, S., et al. "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 of GeparNuevo study." Annals of Oncology 30.8 (2019): 1279-1288.

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