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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, B V; Blohmer, J-U; Grischke, E-M; Furlanetto, J; Tesch, H; Hanusch, C; Engels, K; Rezai, M; Jackisch, C; Schmitt, W D; von Minckwitz, G; Thomalla, J; Kümmel, S; Rautenberg, B; Fasching, P A; Weber, K; Rhiem, K; Denkert, C; Schneeweiss, A.
Afiliación
  • Loibl S; German Breast Group, Neu-Isenburg; Oncological Practice Bethanien, Cancer Center Frankfurt Northeast, Frankfurt am Main. Electronic address: sibylle.loibl@gbg.de.
  • Untch M; HELIOS Klinikum Berlin-Buch, Berlin.
  • Burchardi N; German Breast Group, Neu-Isenburg.
  • Huober J; Brustzentrum, Universitätsfrauenklinik Ulm, Ulm.
  • Sinn BV; Institute of Pathology, Charité-Universitätsmedizin Berlin, Berlin; Berlin Institute of Health (BIH), Berlin.
  • Blohmer JU; Gynäkologie mit Brustzentrum, Charité-Universitätsmedizin Berlin, Berlin.
  • Grischke EM; Universitätsfrauenklinik Tübingen, Tübingen.
  • Furlanetto J; German Breast Group, Neu-Isenburg.
  • Tesch H; Oncological Practice Bethanien, Cancer Center Frankfurt Northeast, Frankfurt am Main.
  • Hanusch C; Rotkreuzklinikum München Frauenklinik, München.
  • Engels K; Zentrum für Pathologie, Zytologie und Molekularpathologie Neuss, Neuss.
  • Rezai M; Medical Center, Luisenkrankenhaus Düsseldorf, Düsseldorf.
  • Jackisch C; Brustzentrum, Sana-Klinikum Offenbach, Offenbach.
  • Schmitt WD; Institute of Pathology, Charité-Universitätsmedizin Berlin, Berlin.
  • von Minckwitz G; German Breast Group, Neu-Isenburg.
  • Thomalla J; Praxisklinik für Hämatologie und Onkologie Koblenz, Koblenz.
  • Kümmel S; Breast Unit, Kliniken Essen-Mitte, Essen.
  • Rautenberg B; Klinik für Frauenheilkunde, Universitätsklinikum Freiburg, Freiburg.
  • Fasching PA; Brustzentrum, Universitätsklinikum Erlangen, Erlangen.
  • Weber K; German Breast Group, Neu-Isenburg.
  • Rhiem K; Center for Hereditary Breast and Ovarian Cancer, University Hospital Cologne, Cologne.
  • Denkert C; Institute of Pathology, Charité-Universitätsmedizin Berlin, Berlin.
  • Schneeweiss A; National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.
Ann Oncol ; 30(8): 1279-1288, 2019 08 01.
Article en En | MEDLINE | ID: mdl-31095287
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.
Asunto(s)
Anticuerpos Monoclonales/administración & dosificación; Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación; Biomarcadores de Tumor/análisis; Terapia Neoadyuvante/métodos; Neoplasias de la Mama Triple Negativas/terapia; Adulto; Anciano; Albúminas/administración & dosificación; Albúminas/efectos adversos; Anticuerpos Monoclonales/efectos adversos; Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos; Antígeno B7-H1/análisis; Antígeno B7-H1/inmunología; Antígeno B7-H1/metabolismo; Biomarcadores de Tumor/genética; Biomarcadores de Tumor/inmunología; Biomarcadores de Tumor/metabolismo; Mama/patología; Mama/cirugía; Ciclofosfamida/administración & dosificación; Ciclofosfamida/efectos adversos; Método Doble Ciego; Epirrubicina/administración & dosificación; Epirrubicina/efectos adversos; Femenino; Humanos; Hipertiroidismo/inducido químicamente; Hipertiroidismo/epidemiología; Hipotiroidismo/inducido químicamente; Hipotiroidismo/epidemiología; Linfocitos Infiltrantes de Tumor/efectos de los fármacos; Linfocitos Infiltrantes de Tumor/inmunología; Linfocitos Infiltrantes de Tumor/metabolismo; Mastectomía; Persona de Mediana Edad; Terapia Neoadyuvante/efectos adversos; Paclitaxel/administración & dosificación; Paclitaxel/efectos adversos; Placebos/administración & dosificación; Placebos/efectos adversos; Estudios Prospectivos; Receptor ErbB-2/análisis; Receptor ErbB-2/genética; Receptor ErbB-2/metabolismo; Glándula Tiroides/efectos de los fármacos; Resultado del Tratamiento; Neoplasias de la Mama Triple Negativas/inmunología; Neoplasias de la Mama Triple Negativas/patología; Adulto Joven
Palabras clave

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Protocolos de Quimioterapia Combinada Antineoplásica / Biomarcadores de Tumor / Terapia Neoadyuvante / Neoplasias de la Mama Triple Negativas / Anticuerpos Monoclonales Tipo de estudio: Clinical_trials / Observational_studies / Risk_factors_studies Idioma: En Revista: Ann Oncol Asunto de la revista: NEOPLASIAS Año: 2019 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Protocolos de Quimioterapia Combinada Antineoplásica / Biomarcadores de Tumor / Terapia Neoadyuvante / Neoplasias de la Mama Triple Negativas / Anticuerpos Monoclonales Tipo de estudio: Clinical_trials / Observational_studies / Risk_factors_studies Idioma: En Revista: Ann Oncol Asunto de la revista: NEOPLASIAS Año: 2019 Tipo del documento: Article