Patients with NSCLC Experience Improved DFS with Pembrolizumab After Surgery


Adjuvant pembrolizumab led to improved disease-free survival versus placebo in patients with fully resected non–small cell lung cancer, according to second interim results from the PEARLS/KEYNOTE-091 trial.

Pembrolizumab (Keytruda) improved disease-free survival (DFS) vs placebo in patients with completely resected early-stage non–small cell lung cancer (NSCLC) regardless of surgical resection, tumor size, or the extent of adjuvant chemotherapy. These data from the second interim analysis of the PEARLS/KEYNOTE-091 study (NCT02504372) were presented at the 2022 American Society of Clinical Oncology Annual Meeting.1

Patients receiving pembrolizumab as adjuvant therapy had a median DFS of 53.6 months (95% CI, 39.2-not reached [NR]) vs placebo with a median DFS of 42 months (95% CI, 31.3-NR; hazard ratio [HR], 0.76; P = .0014). The 18-month DFS rate for patients in the pembrolizumab arm was 73.4% compared with 64.3% in patients in the placebo arm. Less patients experienced DFS events with pembrolizumab (35.9%) vs placebo (44.3%).

Investigators in this global, randomized, triple-blind, phase 3 trial randomized patients 1:1 to receive pembrolizumab (n = 590) or placebo (n = 587). Pembrolizumab was given in 200 mg doses once every 3 weeks for up to 18 administrations. The study had 2 primary end points of DFS across the entire patient population and DFS among patients with a PD-L1 tumor proportion score (TPS) of greater than or equal to 50%. Secondary end points included a PD-L1 TPS of 1% or greater, overall survival (OS), lung cancer-specific survival, and safety. Eligible patients must have had an ECOG performance score of 0 or 1 and be considered for stage IB disease with a tumor of at least 4 cm, or strongly recommended for stage II and stage IIIA disease.

Median DFS in the PD-L1 TPS of 50% or greater population was not reached in both pembrolizumab (n = 168) and placebo (n = 165) arms (HR, 0.82; 95% CI, 0.57-1.18; P = .14). The 18-month DFS rates for the experimental arm was 71.7% vs 70.1% for the control arm. DFS events occurred in 32.1% of patients in the pembrolizumab arm and in 38.2% of patients in the placebo arm.

The median OS was also not reached in both patient groups (HR, 0.87; 95% CI, 0.67-1.15; P = .17). The 18-month OS rates was 91.7% with pembrolizumab and 91.3% with placebo.

The median age of patients was 65 years, and nearly 70% of patients were male. Slightly more than half of patients were from western Europe and the rest were from eastern Europe, Asia, or other parts of the world. In patients receiving pembrolizumab, 35.6% had an ECOG score of 1, as did 41.6% of patients receiving placebo. More than 80% of patients in both treatment arms received adjuvant chemotherapy. Overall, more than half of patients in the pembrolizumab group presented with stage II disease (55.8%), 30.0% of patients had stage IIIA, and 14.2% had stage IB; whereas 57.6% of patients in the placebo group had stage II, 27.6% had stage IIIA, and 14.5% had stage IB. The majority of patients in both arms had a lobectomy: 78.1% in the pembrolizumab arm vs 79.0% in the placebo arm.

The safety profile did not reveal anything unexpected. Grades 3 to 5 adverse events were reported in 34.1% of patients receiving pembrolizumab and in 25.8% of patients receiving placebo.

DFS, OS, and safety data presented in this analysis of the PEARLS/KEYNOTE-091 trial support pembrolizumab’s benefit as an adjuvant therapy for patients with stage IB to stage IIIA NSCLC after complete resection.


O'Brien M, Paz-Ares L, Jha N, et al. EORTC-1416-LCG/ETOP 8-15 – PEARLS/KEYNOTE-091 study of pembrolizumab versus placebo for completely resected early-stage non-small cell lung cancer (NSCLC): outcomes in subgroups related to surgery, disease burden, and adjuvant chemotherapy use. J Clin Oncol. 2022;40 (suppl 16): 8512). doi:10.1200/JCO.2022.40.16_suppl.8512

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