Durvalumab in Combination With Neoadjuvant Chemotherapy in Early Triple-Negative Breast Cancer: Long-Term Analysis From the GeparNuevo Trial
Abstract
The phase II GeparNuevo trial investigated whether adding durvalumab to neoadjuvant chemotherapy (NACT) only in patients with early triple-negative breast cancer cT1b-cT4a-d would improve pathologic complete response (pCR) rate and patient survival. Hundred and seventy-four patients were randomly assigned to receive durvalumab or placebo concurrently with nab-paclitaxel once per week and followed by dose-dense epirubicin and cyclophosphamide. With 86.4 months of median follow-up compared with the previously reported 43.7 months, durvalumab showed sustained significant improvements in long-term outcomes as defined by STEEP compared with placebo regarding not only invasive disease-free survival (iDFS; hazard ratio [HR], 0.56 [95% CI, 0.32 to 0.99]; stratified log-rank P = .0431), but also distant disease-free survival (DDFS; HR, 0.41 [95% CI, 0.21 to 0.80]; P = .0069) and overall survival (OS; HR, 0.33 [95% CI, 0.14 to 0.79]; P = .0085). All analyses were stratified by stromal tumor-infiltrating lymphocytes (sTILs) at baseline (low [≤10%], intermediate [11%-59%], high [≥60%]). In exploratory subgroup analysis, patients with nodal involvement at baseline demonstrated a greater iDFS benefit (HR, 0.33 [95% CI, 0.144 to 0.771]; P = .01; P interaction = 0.045). sTILs in residual disease (RD) could be assessed in 39/71 patients without pCR. Post hoc analyses by sTILs high (>10%) versus low (≤10%) in RD showed estimated 7-year iDFS rates of 92.3% (95% CI, 56.6 to 98.9) and 51.4% (95% CI, 29.2 to 69.7), respectively. Hence, adding durvalumab to dose-dense NACT without adjuvant continuation of checkpoint inhibition improved long-term survival outcomes, irrespective of the extent of pathologic response. This underscores the necessity to re-evaluate the adjuvant continuation of checkpoint inhibition.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (20)
Sibylle Loibl
Johann Wolfgang Goethe Universität, Frankfurt am Main, Germany
Michael Untch
From the National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation (C.E.G., E.P.M., N.W., P.R., I.L.W., A.M.B.) and University of Pittsburgh School of Medicine–UPMC Hillman Cancer Center (C.E.G., N.W., P.R., A.M.B.) — both in Pittsburgh; AGO-B and Helios Klinikum Berlin–Buch, Berlin (M.U.), the National Center for Tumor Diseases, Heidelberg University Hospital, and German Cancer Research Center, Heidelberg (A.S.), Evangelische Kliniken Gelsenkirchen, Gelsenkirchen (H.H.F.), Arbeitsgemeinschaft Gynäkologische Onkologie–Breast and Sana Klinikum Offenbach, Offenbach (C.J.), the Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen–EMN, Friedrich–Alexander University Erlangen–Nuremberg, Erlangen (P.A.F.), German Breast Group, Neu-Isenburg (P.W., S.L.), and the Center for Hematology and Oncology Bethanien, Goethe University, Frankfurt (S.L.) — all in Germany; National Taiwan University Hospital and National Taiwan University College of Medicine,...
Jens Huober
Breast Center, Kantonsspital St Gallen, St Gallen, Switzerland
Vanessa Schaser
GBG c/o GBG Forschungs GmbH, Neu-Isenburg, Germany
Michael Braun
Carsten Denkert
Institute of Pathology, Philipps University Marburg and University Hospital Marburg (UKGM), Marburg, Germany
Andreas Hartkopf
Jens-Uwe Blohmer
Gynäkologie mit Brustzentrum, Charité-Univesitätsmedizin Berlin, Berlin, Germany
Claus Hanusch
Rotkreuzklinikum München, München, Germany
Theresa Link
Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
Mattea Reinisch
Breast Unit, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany
Dirk-Michael Zahm
SRH Wald-Klinikum Gera, Gera, Germany
Rudolf Weide
Vesna Bjelic-Radisic
Department of Senology, Breast Center, Helios University Clinic Wuppertal, Wuppertal, Germany
Peter Staib
4Department of Haematology and Oncology, St. Antonius Krankenhaus Eschweiler, Eschweiler, Germany
Hans Tesch
Centrum für Hämatologie und Onkologie am Bethanien-Krankenhaus, Frankfurt am Main, Germany
Kerstin Rhiem
Ralf Lorenz
Studien GbR Braunschweig, Braunschweig, Germany
Julia Rey
GBG c/o GBG Forschungs GmbH, Neu-Isenburg, Germany
Andreas Schneeweiss
National Center for Tumor Diseases, University Hospital and German Cancer Research Center, Heidelberg, Germany