Neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for high-risk early-stage TNBC: Final analysis results from the phase 3 KEYNOTE-522 study.
Abstract
507 Background: KEYNOTE-522 (NCT03036488) showed statistically significant and clinically meaningful improvements in pCR, EFS, and OS with the addition of pembrolizumab (pembro) to chemotherapy (chemo) in participants (pts) with high-risk early-stage TNBC. Here, we present updated results from the final analysis. Methods: Eligible pts with previously untreated, non-metastatic, centrally confirmed TNBC (stage T1c N1-2 or T2-4 N0-2 per AJCC) were randomized 2:1 to neoadjuvant pembro 200 mg Q3W or placebo (pbo), both given with 4 cycles of paclitaxel + carboplatin, then 4 cycles of doxorubicin or epirubicin + cyclophosphamide. After definitive surgery, pts received adjuvant pembro or pbo for 9 cycles or until recurrence or unacceptable toxicity. Dual primary endpoints are pCR (ypT0/Tis ypN0) and EFS (time from randomization to disease progression that precluded definitive surgery, local/distant recurrence, second primary cancer, or death from any cause); OS is the key secondary endpoint. Results: 1174 pts were randomized to pembro (n = 784) or pbo (n = 390). At the data cutoff date (October 14, 2025), median follow-up (range) was 93.8 mo (84.7-102.8). The 7-yr EFS rate (95% CI) was 78.3% (75.3-81.1) in the pembro group vs 69.8% (65.0-74.2) in the pbo group; the HR was 0.68 (95% CI, 0.54-0.86). The 7-yr OS rate (95% CI) was 85.1% (82.5-87.5) in the pembro group vs 77.2% (72.7-81.1) in the pbo group; the HR was 0.64 (95% CI, 0.49-0.85). The benefit of pembro on EFS and OS was generally consistent across most prespecified subgroups, including those defined by PD-L1 expression, nodal status, and disease stage. Rates of grade ≥3 treatment-related AEs were 77.1% in the pembro group and 73.3% in the pbo group (death incidence, 0.5% vs 0.3%, respectively); rates of any grade immune-mediated AEs were 35.0% vs 13.1%, respectively. Conclusions: After a median follow-up of 7.8 years, neoadjuvant pembro + chemo followed by adjuvant pembro continues to show a clinically meaningful survival benefit compared with neoadjuvant chemo alone in pts with high-risk early-stage TNBC. Clinical trial information: NCT03036488 .
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (19)
Peter Schmid
Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, London
Javier Cortés
International Breast Cancer Center, Pangaea Oncology, Quiron Group, Barcelona
Rebecca Alexandra Dent
Department of Medical Oncology, National Cancer Center Singapore, Singapore, and Duke-NUS Medical School, Singapore, Singapore
Heather L. McArthur
UT Southwestern Medical Center, Dallas, TX
Lajos Pusztai
Sherko Kuemmel
Breast Unit, Kliniken Essen Mitte Evangelische Huyssens-Stiftung, Essen, Germany
Carsten Denkert
Institute of Pathology, Philipps University Marburg and University Hospital Marburg (UKGM), Marburg, Germany
Yeon Hee Park
Rina Hui
School of Clinical Medicine, Hong Kong University Health System
Nadia Harbeck
Breast Center, Department of Obstetrics and Gynecology and Comprehensive Cancer Center Munich, Ludwig Maximilians University Munich University Hospital, Munich, Germany
Masato Takahashi
Seock-Ah Im
Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea
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,...
Peter A. Fasching
Fatima Cardoso
Surui Hou
Oncology, Merck & Co., Inc., Rahway, NJ
Usha Malhotra
Oncology, Merck & Co., Inc., Rahway, NJ
Francisco Beca
Harvard Medical School Initiative for RNA Medicine, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School
Joyce O'Shaughnessy
Baylor University Medical Center, Texas Oncology, Sarah Cannon Research Institute, Dallas, TX