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      Durvalumab improves long-term outcome in TNBC: results from the phase II randomized GeparNUEVO study investigating neodjuvant durvalumab in addition to an anthracycline/taxane based neoadjuvant chemotherapy in early triple-negative breast cancer (TNBC).

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          Abstract

          506

          Background: The GeparNuevo trial investigated the addition of durvalumab, an anti-PD-L1 checkpoint inhibitor (CPI), to standard neoadjuvant chemotherapy (NACT) in patients with early TNBC. Durvalumab increased the pathological complete response (pCR) rate particularly in patients treated with durvalumab alone before start of chemotherapy (Loibl et al. Ann Oncol 2019). Methods: GeparNuevo randomized patients with cT1b-cT4a-d tumors and centrally confirmed TNBC to durvalumab (D) 1.5 g i.v. or placebo every 4 weeks. D/placebo monotherapy (0.75 g i.v.) was given for the first 2 weeks (window phase), followed by D/placebo plus nab-paclitaxel 125 mg/m² weekly for 12 weeks, followed by D/placebo plus epirubicin/cyclophosphamide (EC) q2 weeks for 4 cycles. Randomization was stratified by stromal tumor infiltrating lymphocytes (sTILs) (low (≤10%), intermediate (11-59%), high (≥60%)). The primary objective was pCR (ypT0 ypN0). Secondary time-to-event endpoints included invasive disease-free survival (iDFS), distant disease-free survival (DDFS) and overall survival (OS). Results: A total of 174 patients were enrolled between June 2016 and September 2017. The pCR rate with durvalumab was 53.4% versus placebo 44.2% (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). After a median follow-up of 42.2 months, 34 events occurred in 174 patients. 3-year iDFS in pCR vs non pCR was 92.0% vs 71.9% (log-rank p = 0.002). 3-year iDFS was 84.9% with durvalumab vs 76.9% with placebo (HR 0.54, 95%CI 0.27-1.09, stratified log-rank p = 0.0559); 3-year DDFS 91.4% vs 79.5% (HR 0.37, 95%CI 0.15-0.87, p = 0.0148); 3-year OS 95.1% vs 83.1% (HR 0.26, 95%CI 0.09-0.79, p = 0.0076). No difference was seen in iDFS, DDFS and OS between the window and no window cohort. Conclusions: Durvalumab added to neoadjuvant chemotherapy in TNBC significantly improved long-term outcome despite a small pCR increase and no continuation after surgery. It needs to be questioned whether adjuvant therapy with CPI is needed at all. Clinical trial information: NCT02685059.

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          Author and article information

          Journal
          Journal of Clinical Oncology
          JCO
          American Society of Clinical Oncology (ASCO)
          0732-183X
          1527-7755
          May 20 2021
          May 20 2021
          : 39
          : 15_suppl
          : 506
          Affiliations
          [1 ]German Breast Group (GBG), Neu-Isenburg, Germany;
          [2 ]University Hospital and German Cancer Research Center Heidelberg, Heidelberg, Germany;
          [3 ]Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Ulm, Ulm, Germany;
          [4 ]Rotkreuzklinikum, Munich, Germany;
          [5 ]Gynäkologie mit Brustzentrum Charité-Universitätsmedizin, Berlin, Germany;
          [6 ]SRH Waldklinikum Gera GmBH, Gera, Germany;
          [7 ]Rotkreuzklinikum, Frauenklinik, Munich, Germany;
          [8 ]Praxis fuer Haematologie und Onkologie, Koblenz, Germany;
          [9 ]Sana Klinikum, Offenbach, Germany;
          [10 ]St. Antonius Hospital, Eschweiler, Germany;
          [11 ]TU Dresden, Dresden, Germany;
          [12 ]Center for Familial Breast and Ovarian Cancer and Center for Integrated Oncology (CIO), Medical Faculty, University of Cologne and University Hospital Cologne, Cologne, Germany;
          [13 ]University Hospital Frankfurt, Frankfurt Am Main, Germany;
          [14 ]Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany;
          [15 ]Institute of Pathology, Philipps-University Marburg and University Hospital Marburg, Marburg, Germany;
          [16 ]Helios Klinikum Berlin-Buch, Berlin, Germany;
          Article
          10.1200/JCO.2021.39.15_suppl.506
          e86d9610-308c-42a1-b3b8-1e8986d888f5
          © 2021
          History

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