Lopes G, et al. - Given that PFS and OS were significantly improved by pembrolizumab vs chemotherapy when used as first-line therapy for metastatic NSCLC without targetable alterations and PD-L1 TPS ≥ 50% in KEYNOTE-024, researchers compared pembrolizumab with chemotherapy at the lower TPS of ≥ 1% in KEYNOTE-042. For the first time, it was demonstrated that, vs platinum-based chemotherapy, pembrolizumab provided better outcomes, including OS, in patients with previously untreated advanced/metastatic NSCLC without sensitizing EGFR or ALK alterations and a PD-L1 TPS ≥ 1%. For PD-L1-expressing advanced/metastatic NSCLC, the role of pembrolizumab monotherapy as a standard first-line treatment was corroborated.

Methods

• In a randomized 1:1 manner, researchers assigned eligible patients to receive ≤ 35 cycles of pembrolizumab 200 mg Q3W or investigator’s choice of ≤ 6 cycles of paclitaxel + carboplatin or pemetrexed + carboplatin with optional pemetrexed maintenance (nonsquamous only).
• Stratification of randomization by region (east Asia vs non-east Asia), ECOG PS (0 vs 1), histology (squamous vs nonsquamous), and TPS (≥ 50% vs 1-49%) was done.
• OS in patients with TPS ≥ 50%, ≥ 20%, and ≥ 1% were included as primary end-points.
• They used the stratified log-rank test to evaluate OS differences.
• At the prespecified second interim analysis, the efficacy boundaries were one-sided P=.0122, .01198, and .01238, respectively.

Results

• Randomization of 1,274 patients was performed, with 637 in each arm.
• Data showed 599 patients (47.0%) had TPS ≥ 50%, 818 (64.2%) had TPS ≥ 20%.
• Pembrolizumab was still being taken by 13.7% of patients and 4.9% were receiving pemetrexed maintenance after 12.8 months of follow-up.
• In patients with TPS ≥ 50% (HR 0.69), TPS ≥ 20% (HR 0.77), and TPS ≥ 1% (HR 0.81), significantly improved OS was seen in patients taking pembrolizumab.
• Pembrolizumab carried less frequent grade 3-5 drug-related AEs (17.8% vs 41.0%).