The addition of pembrolizumab to stereotactic body radiotherapy (SBRT) did not improve event-free survival (EFS) or overall survival (OS) in patients with unresected stage I or II non-small cell lung cancer (NSCLC), according to data from the phase 3 KEYNOTE-867 trial presented at the 2024 ESMO Immuno-Oncology Congress. The study's findings led to its early termination due to an unfavorable benefit-risk profile.
In the KEYNOTE-867 trial, 448 patients with previously untreated, unresected, biopsy-confirmed stage I or II NSCLC who were unable or unwilling to undergo thoracic surgery were randomized to receive either pembrolizumab (200 mg every 3 weeks) plus SBRT or placebo plus SBRT for 17 cycles. SBRT dosing varied based on tumor location. The primary endpoint was EFS, and secondary endpoints included OS, time to death or distant metastases, safety, and quality of life.
Efficacy Outcomes
After a median follow-up of 20.6 months, the median EFS was 31.2 months (95% CI, 22.5-39.1) in the pembrolizumab arm compared to 28.3 months (95% CI, 19.8-33.1) in the placebo arm (HR, 0.92; 95% CI, 0.69-1.24; stratified log-rank P = .29). The median OS was 54.7 months (95% CI, 33.5-NR) in the pembrolizumab arm versus not reached (95% CI, 44.4-NR) in the placebo arm (HR, 1.33; 95% CI, 0.93-1.90).
Subgroup analysis showed a trend favoring pembrolizumab in patients under 65 years of age for both EFS (HR, 0.44; 95% CI, 0.18-1.24) and OS (HR, 0.53; 95% CI, 0.18-1.56). However, this trend was not observed in patients 65 years of age or older.
Safety and Tolerability
Treatment-related adverse events (TRAEs) of any grade were more common in the pembrolizumab arm (73.5%) compared to the placebo arm (50.0%). Grade 3 or higher TRAEs occurred in 20.4% and 3.7% of patients, respectively. Serious TRAEs were reported in 14.2% and 2.3% of patients, respectively. TRAEs led to treatment discontinuation in 15.9% of patients in the pembrolizumab arm and 2.3% in the placebo arm. Treatment-related deaths occurred in 2.2% of patients in the pembrolizumab arm.
The most common any-grade TRAEs in the pembrolizumab arm included hypothyroidism (13.7%), rash (12.4%), pruritus (11.9%), fatigue (11.5%), and pneumonitis (9.7%). Immune-mediated adverse events were also more frequent in the pembrolizumab arm (38.5%) compared to the placebo arm (11.5%).
Andreas Pircher, MD, PhD, of the Medical University of Innsbruck in Austria, noted that the KEYNOTE-867 trial was stopped based on the benefit:risk profile assessed during an interim analysis.
