Adjuvant pembrolizumab significantly improves disease-free survival (DFS) compared to placebo in patients with early-stage non–small cell lung cancer (NSCLC) who have undergone complete resection, according to findings from the phase 3 PEARLS/KEYNOTE-091 (PEARLS) study.
Patients in the pembrolizumab arm demonstrated median DFS nearly 12 months longer than those in the placebo arm (53.6 vs. 42.0 months). Investigators observed a DFS benefit for patients with any programmed death-ligand 1 (PD-L1) expression.
“We believe that pembrolizumab has the potential to become a new adjuvant treatment option for patient with [stage IB to IIIA] non–small cell lung cancer following complete resection and adjuvant chemotherapy when recommended,” concluded first author Luis Paz-Ares, MD, chair of the clinical research unit at Hospital Universitario 12 de Octubre, CNIO & Universidad Complutense, Madrid. “Pembrolizumab provided a benefit regardless of pathological stage and PD-L1 progression subgroup.”
The findings were presented by Dr. Paz-Ares at the European Society for Medical Oncology (ESMO) March virtual plenary session and published March 17 in Annals of Oncology.
Pembrolizumab is the standard treatment for patients with advanced NSCLC, but its efficacy in early-stage disease remains unclear. To determine whether patients with early-stage disease benefit from pembrolizumab, Dr. Paz-Ares and colleagues randomized 1,177 adults with stage IB, II, or IIIA NSCLC to 200 mg of pembrolizumab (n = 590) or placebo (n = 587) every 3 weeks.
All patients had Eastern Cooperative Oncology Group performance status of 0-1, and any level of PD-L1 expression. Of the study participants, 168 in the pembrolizumab arm and 165 in the placebo arm had PD-L1 expression and a tumor proportion score (TPS) of at least 50%.
Overall, patients receiving pembrolizumab had a DFS of 53.6 months compared to 42.0 months in the placebo arm (hazard ratio [HR], 0.76; P = .0014). The DFS benefit was generally consistent across patients with PD-L1 TPS <1%, 1%-49%, and ≥50%. In the subset of patients with PD-L1 TPS ≥50%, a slightly higher percentage of patients in the pembrolizumab group demonstrated DFS at 18 months (71.7% vs. 70.2%), but the difference did not reach statistical significance (HR, 0.82; P = .14).
Overall survival (OS) at 18 months was 91.7% in the treatment arm and 91.3% in the placebo arm (HR, 0.87; P = .17), but the data were immature.
“The disease-free survival benefit was observed across most prespecified subgroups,” Dr. Paz-Ares said.
No new safety concerns were raised. Grade 3 or greater adverse events occurred in 34.1% of patients in the treatment arm and 25.8% in the placebo arm. Adverse events led to discontinuation in 19.8% of patients receiving pembrolizumab and 5.9% of patients in the placebo group.
Invited discussant Martin Reck, MD, said these findings represent forward progress. “We do see many patients with distant relapse, which indicates that we have to improve our control of the systemic relapse,” said Dr. Reck, head of the department of thoracic oncology and the clinical trial department at the Lungen Clinic Grosshansdorf, Germany.
Prior data provide a rationale for using immune checkpoint inhibition in early-stage NSCLC, and both the PEARLS study and the IMpower010 trial evaluating atezolizumab in a similar setting have demonstrated relevant improvements in DFS.
“I think we are entering the times of perioperative immunotherapies. We are seeing the first signals of efficacy for adjuvant immunotherapy in two large, randomized trials,” Dr. Reck said.
Based on the PEARLS trial results, Dr. Reck said that PD-L1 appears to have predictive and prognostic value but noted that “several other clinical trials say PD-L1 expression is a poor prognostic marker” for sensitivity to immune checkpoint inhibitor. Given this potential inconsistency, Dr. Reck called for further follow-up in this patient population and for studies in larger groups of patients to further delineate the role of PD-L1 as well as EGFR mutations and adjuvant chemotherapy in patients with early NSCLC.
The PEARLS study was funded by Merck Sharp & Dohme Corp. Dr. Paz-Ares and Dr. Reck disclosed numerous relationships with pharmaceutical companies.