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
In brief
Pembrolizumab did not improve event-free survival after stereotactic radiation for lung cancer
In 448 people with inoperable early-stage lung cancer or who declined surgery, adding pembrolizumab to stereotactic radiation did not meaningfully improve event-free survival: median results were 31.2 months versus 28.3 months with radiation alone. Severe treatment-related side effects were more common, and five people died from treatment in the pembrolizumab group; the trial was stopped early.
- Journal
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology (Q1)
- Published
- 28 October 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Salma K Jabbour, Szabolcs Sótér, Michael Eaton, Gabriella Gálffy, Dariusz Kowalski, Akito Hata, et al.
- PMID
- 42950173
- DOI
- 10.1200/JCO-26-00404
Why clinicians should know about it
- Picked for Oncology and Radiation Oncology (paper of the day, 29 October 2026): Phase III RCT of SBRT + pembrolizumab vs SBRT alone
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 8th 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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.