KEYNOTE-867: A Phase III, Randomized, Double-Blind Study of Stereotactic Body Radiotherapy With Pembrolizumab for Unresected Stage I or II Non–Small Cell Lung Cancer
Year: 2026
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: Purpose Stereotactic body radiotherapy (SBRT) is standard of care for inoperable stage I or II non–small cell lung cancer (NSCLC). KEYNOTE-867 (ClinicalTrials.gov identifier: NCT03924869 ) evaluated the addition of pembrolizumab to SBRT in participants diagnosed with stage I or II NSCLC that was inoperable or in participants who refused surgery. Methods Adults with untreated, stage I or II (T1 to limited T3, N0, M0) NSCLC (AJCC 8 th edition) that was inoperable, or adults who refused surgery, were randomly assigned 1:1 to thoracic SBRT to primary tumors for ≤2 weeks concomitantly with pembrolizumab 200 mg or placebo once every 3 weeks for ≤17 cycles. The primary end point was event-free survival (EFS) by blinded independent central review. Results A total of 448 participants were randomly assigned to SBRT plus pembrolizumab (n = 227) or SBRT plus placebo (n = 221). The median time from random assignment to the data cutoff date (June 11, 2024) for the prespecified first interim analysis was 20.6 (range, 1.3-56.8) months. The median EFS (95% CI) was 31.2 (22.5 to 39.1) months and 28.3 (19.8 to 33.1) months for the pembrolizumab and placebo arms, respectively (hazard ratio, 0.92 [95% CI, 0.69 to 1.24]; P = .2932). Among participants who received ≥1 dose of study treatment, grade 3-5 treatment-related adverse events (AEs) occurred in 46/226 (20.4%) participants in the pembrolizumab arm and 8/218 (3.7%) participants in the placebo arm. There were five treatment-related deaths all of which occurred in the pembrolizumab arm (2.2%). Conclusion The addition of pembrolizumab to SBRT did not improve EFS and was associated with a higher incidence of treatment-related AEs compared with SBRT alone in participants with inoperable stage I or II NSCLC. Based on the benefit-risk profile, the KEYNOTE-867 trial was prematurely stopped, and all study treatment was discontinued.
Source: Journal of Clinical Oncology
DOI: 10.1200/jco-26-00404
Authors: Salma K. Jabbour, Szabolcs Sótér, Michael Eaton, Gabriella Gálffy, Dariusz Kowalski, Akito Hata, Augusto Valdivia, Nikolaj Frost, Evgeny Levchenko, Mariana Monteiro, Anoop Haridass, Myriam Bouchard, Ki Hyeong Lee, Myung-Ju Ahn, Brett G.M. Hughes, André Durham, Yan Xu, Ayman Samkari, Andrew Song, Andreas Pircher
Institutions: Rutgers, The State University of New Jersey, Rutgers Cancer Institute, Országos Korányi Tbc és Pulmonológiai Intézet, Franciscan Health Indianapolis, The Maria Sklodowska-Curie National Research Institute of Oncology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institute of Oncology, Charité – Universitätsmedizin Berlin, Institute of Oncology NN Petrov, Clatterbridge Cancer Centre NHS Foundation Trust, Centre Hospitalier Universitaire de Sherbrooke, Chungbuk National University Hospital, Samsung Medical Center, Sungkyunkwan University, The University of Queensland, Royal Brisbane and Women's Hospital, University Hospital of Geneva, Merck & Co., Inc., Rahway, NJ, USA (United States), Innsbruck Medical University, Universität Innsbruck
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7224084630