Overall Survival with Pembrolizumab in Early-Stage Triple-Negative Breast Cancer

Peter Schmid; Javier Cortes; Rebecca Dent; Heather McArthur; Lajos Pusztai; Sherko Kümmel; Carsten Denkert; Yeon Hee Park; Rina Hui; Nadia Harbeck; Masato Takahashi; Seock-Ah Im; Michael Untch; Peter A Fasching; Marie-Ange Mouret-Reynier; Theodoros Foukakis; Marta Ferreira; Fatima Cardoso; Xuan Zhou; Vassiliki Karantza; Konstantinos Tryfonidis; Gursel Aktan; Joyce O'Shaughnessy; KEYNOTE-522 Investigators

doi:10.1056/NEJMoa2409932

Overall Survival with Pembrolizumab in Early-Stage Triple-Negative Breast Cancer

N Engl J Med. 2024 Sep 15. doi: 10.1056/NEJMoa2409932. Online ahead of print.

Authors

Peter Schmid¹, Javier Cortes¹, Rebecca Dent¹, Heather McArthur¹, Lajos Pusztai¹, Sherko Kümmel¹, Carsten Denkert¹, Yeon Hee Park¹, Rina Hui¹, Nadia Harbeck¹, Masato Takahashi¹, Seock-Ah Im¹, Michael Untch¹, Peter A Fasching¹, Marie-Ange Mouret-Reynier¹, Theodoros Foukakis¹, Marta Ferreira¹, Fatima Cardoso¹, Xuan Zhou¹, Vassiliki Karantza¹, Konstantinos Tryfonidis¹, Gursel Aktan¹, Joyce O'Shaughnessy¹; KEYNOTE-522 Investigators

Affiliation

¹ From the Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, London (P.S.); International Breast Cancer Center, Pangaea Oncology, Quirónsalud Group, and Medical Scientia Innovation Research, Barcelona, and IOB Madrid, Institute of Oncology, Hospital Beata María Ana, and the Faculty of Biomedical and Health Sciences, Department of Medicine, Universidad Europea de Madrid, Madrid - all in Spain (J.C.); National Cancer Center Singapore, Duke-National University of Singapore Medical School, Singapore (R.D.); University of Texas Southwestern Medical Center (H.M.) and Baylor University Medical Center, Texas Oncology, Sarah Cannon Research Institute (J.O.) - both in Dallas; Yale School of Medicine, Yale Cancer Center, New Haven, CT (L.P.); the Breast Unit, Department of Gynecology with Breast Center, Kliniken Essen-Mitte, Essen (S.K.), Charité-Universitätsmedizin Berlin (S.K.) and the Breast Cancer Center, Helios Klinikum Berlin-Buch (M.U.), Berlin, the Institute of Pathology, Philipps University of Marburg and University Hospital Marburg, Marburg (C.D.), the Breast Center, Department of Obstetrics and Gynecology and Comprehensive Cancer Center Munich, LMU University Hospital, Munich (N.H.), and University Hospital Erlangen, Comprehensive Cancer Center Erlangen-European Metropolitan Region of Nuremberg, Erlangen (P.A.F.) - all in Germany; Samsung Medical Center, Sungkyunkwan University School of Medicine (Y.H.P.), and Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University (S.-A.I.) - both in Seoul, South Korea; Westmead Breast Cancer Institute, Westmead Hospital and the University of Sydney, Sydney (R.H.); the Center of Cancer Medicine, School of Clinical Medicine, University of Hong Kong, Hong Kong (R.H.); Hokkaido University Hospital, Sapporo, Japan (M.T.); Centre Jean-Perrin, Clermont-Ferrand, France (M.-A.M.-R.); the Department of Oncology-Pathology, Karolinska Institutet, and Breast Center, Theme Cancer, Karolinska University Hospital, Stockholm (T.F.); Instituto Português de Oncologia do Porto Francisco Gentil, Porto (M.F.), and the Breast Unit, Champalimaud Clinical Center-Champalimaud Foundation, Lisbon (F.C.) - both in Portugal; and the Department of Oncology, Merck, Rahway, NJ (X.Z., V.K., K.T., G.A.).

PMID: 39282906
DOI: 10.1056/NEJMoa2409932

Abstract

Background: In patients with early-stage triple-negative breast cancer, the phase 3 KEYNOTE-522 trial showed significant improvements in pathological complete response and event-free survival with the addition of pembrolizumab to platinum-containing chemotherapy. Here we report the final results for overall survival.

Methods: We randomly assigned, in a 2:1 ratio, patients with previously untreated stage II or III triple-negative breast cancer to receive neoadjuvant therapy with four cycles of pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks plus paclitaxel and carboplatin, followed by four cycles of pembrolizumab or placebo plus doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. After definitive surgery, patients received adjuvant pembrolizumab (pembrolizumab-chemotherapy group) or placebo (placebo-chemotherapy group) every 3 weeks for up to nine cycles. The primary end points were pathological complete response and event-free survival. Overall survival was a secondary end point.

Results: Of the 1174 patients who underwent randomization, 784 were assigned to the pembrolizumab-chemotherapy group and 390 to the placebo-chemotherapy group. At the data-cutoff date (March 22, 2024), the median follow-up was 75.1 months (range, 65.9 to 84.0). The estimated overall survival at 60 months was 86.6% (95% confidence interval [CI], 84.0 to 88.8) in the pembrolizumab-chemotherapy group, as compared with 81.7% (95% CI, 77.5 to 85.2) in the placebo-chemotherapy group (P = 0.002). Adverse events were consistent with the established safety profiles of pembrolizumab and chemotherapy.

Conclusions: Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab resulted in a significant improvement, as compared with neoadjuvant chemotherapy alone, in overall survival among patients with early-stage triple-negative breast cancer. (Funded by Merck Sharp and Dohme, a subsidiary of Merck [Rahway, NJ]; KEYNOTE-522 ClinicalTrials.gov number, NCT03036488.).

Associated data

ClinicalTrials.gov/NCT03036488

Grants and funding

N/A/Merck