Perioperative pembrolizumab in patients with early-stage non-small cell lung cancer (NSCLC) leads to a significant improvement in event-free survival, but not overall survival, according to the findings of a recent randomised, placebo-controlled clinical trial.
Existing evidence points to an event-free survival benefit from using neoadjuvant durvalumab, an anti-programmed cell death-1 agent in resectable stage NSCLC. However, whether similar advantages would arise from the perioperative and adjuvant usage of pembrolizumab, a programmed cell death protein 1 inhibitor, in early stage NSCLC is uncertain.
Recently, an international research group published a randomised, placebo-controlled trial in the New England Journal of Medicine, to evaluate perioperative pembrolizumab in patients with early-stage NSCLC.
Eligible participants had resectable stage NSCLC and were randomised 1:1 to either perioperative pembrolizumab (200 mg) or placebo once every three weeks, with cisplatin-based chemotherapy. This was followed by surgery and then adjuvant pembrolizumab (200 mg) or placebo once every three weeks.
A dual primary endpoint of event-free survival and overall survival was used, with secondary endpoints of a major pathological response, pathological complete response and safety.
Event-free survival findings
A total of 797 participants, of whom 397 were assigned to the pembrolizumab group, were included in the analysis.
The median time from randomisation to the data-cut-off date was 25.2 months. Event-free survival at 24 months was significantly higher in the pembrolizumab group compared to placebo (hazard ratio, HR, for progression, recurrence or death = 0.58, 95% CI 0.46 – 0.72, p < 0.001). In contrast, the estimated 24-month overall survival was not significantly different to placebo.
A major pathological response occurred in a significantly higher proportion of participants assigned to perioperative pembrolizumab (p < 0.0001). Similarly, there was a significantly higher pathological complete response (p = 0.0001).
Any treatment-related adverse events cross the treatment phases were reported in a similar proportion of patients (96.7% vs 95%, pembrolizumab vs placebo).