Pembrolizumab Plus SBRT Fails to Improve EFS in Early-Stage NSCLC

Adding pembrolizumab to stereotactic body radiotherapy (SBRT) did not improve event-free survival (EFS) and increased treatment-related toxicity in patients with unresected stage I or II non–small cell lung cancer (NSCLC), according to results of the phase 3 KEYNOTE-867 trial published in the Journal of Clinical Oncology.

SBRT is standard of care for inoperable stage I or II NSCLC, but rates of recurrence after SBRT, including distant recurrences, are considerable, the investigators noted. The randomized, double-blind trial, supported by Merck Sharp & Dohme, was stopped for futility at its first interim analysis.

The trial randomly assigned 448 adults with untreated stage I or II NSCLC that was inoperable, or who refused surgery, to SBRT plus pembrolizumab 200mg or SBRT plus placebo every 3 weeks for up to 17 cycles. The median age was 73 years. With a median of 20.6 months from randomization to data cutoff, median EFS was 31.2 months with pembrolizumab and 28.3 months with placebo, a difference that was not statistically significant (hazard ratio, 0.92; 95% CI, 0.69-1.24).

Overall survival (OS) also was not improved; deaths occurred in 30.4% of the pembrolizumab arm and 24.4% of the placebo arm, and the point estimate did not favor pembrolizumab (hazard ratio, 1.33; 95% CI, 0.93-1.90). Because EFS was not significant, OS was not formally tested. Grade 3-5 treatment-related adverse events occurred in 20.4% of participants receiving pembrolizumab and 3.7% receiving placebo. All 5 treatment-related deaths (2.2%) occurred in the pembrolizumab arm. All-cause pneumonitis was more frequent with pembrolizumab (20.8% vs 10.6%), whereas radiation pneumonitis rates were similar.

Subgroup and post hoc analyses suggested possible EFS and OS benefit in participants younger than 65 years, but this group made up less than 15% of the population, confidence intervals were wide, and the trial was not designed to assess outcomes by age. Based on the benefit-risk profile, the trial was stopped and all study treatment discontinued, the investigators reported.

Source: Jabbour SK, Sótér S, Eaton M, et al. 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. J Clin Oncol. Published online October 28, 2026. doi:10.1200/JCO-26-00404