An interim analysis of the phase III KEYNOTE-867 trial published by Jabbour et al in the Journal of Clinical Oncology did not appear to support the combination of stereotactic body radiotherapy (SBRT) and pembrolizumab in patients with unresected stage I or II non–small cell lung cancer (NSCLC).
“[Event-free survival] and [overall survival] were not improved with the addition of pembrolizumab to SBRT, and the combination was associated with greater toxicity, compared with SBRT alone,” the investigators wrote.
KEY POINTS
- An interim analysis of KEYNOTE-867 showed that the addition of pembrolizumab to SBRT did not improve event-free or overall survival in patients with unresected stage I or II NSCLC.
- The incidence of treatment-related adverse events, including those of grades 3 to 5, was higher with pembrolizumab vs placebo.
- The findings did not appear to support the use of pembrolizumab in combination with SBRT in this patient population, and the trial was prematurely terminated with all study treatment discontinued.
Study Details
A total of 448 patients with untreated stage I or II NSCLC whose disease was deemed inoperable or who declined surgery were randomly assigned 1:1 to receive thoracic SBRT to the primary tumor over 2 weeks in combination with either 200 mg of pembrolizumab or placebo every 3 weeks for up to 17 cycles.
The primary endpoint was blinded independent central review–assessed event-free survival. Overall survival and safety and tolerability were evaluated as secondary endpoints.
At the prespecified first interim analysis, the median follow-up from randomization was 20.6 months.
Key Findings
Median event-free survival was 31.2 months with pembrolizumab and 28.3 months with placebo (hazard ratio [HR] = 0.92, 95% confidence interval [CI] = 0.69–1.24; P = .2932). Similarly, no overall survival benefit was observed with pembrolizumab (median, 54.7 months vs not reached; HR = 1.33, 95% CI = 0.93–1.90).
Among patients who received at least one dose of study treatment, 20.4% and 3.7% in the pembrolizumab and placebo arms, respectively, experienced grade 3 to 5 treatment-related adverse events. Five treatment-related deaths were reported, all of which occurred in the pembrolizumab arm (2.2%).
“Based on the benefit-risk profile, the KEYNOTE-867 trial was prematurely stopped, and all study treatment was discontinued,” the investigators concluded.
Salma K. Jabbour, MD, of Rutgers Cancer Institute, Rutgers University, New Brunswick, New Jersey, is the corresponding author of the article in the Journal of Clinical Oncology.
Disclosure: The study was supported by Merck Sharp & Dohme. For full disclosures of the study authors, visit ascopubs.org.
