According to an abstract published in the Journal of Immunotherapy of Cancer, a 5-year follow-up of pembrolizumab monotherapy for patients with PD-L1 positive, locally advanced, or metastatic non-small-cell lung cancer without EGFR/ALK alterations showed higher overall survival rates as well as a durable response when compared to chemotherapy.

KEYNOTE-042 was a global, randomized, phase 3 clinical trial that showed that pembrolizumab significantly improved overall survival when compared to platinum-based chemotherapy in patients with locally advanced or metastatic non-small-cell lung cancer. These patients did not have sensitizing EGR/ALK alterations and had PD-L1 tumor proportion scores of ≥50%, ≥20%, and ≥1%. 

Patients were randomized 1:1 to receive either pembrolizumab 200 mg every 3 weeks for 35 cycles or chemotherapy (carboplatin + paclitaxel or pemetrexed) every 3 weeks for 4-6 cycles. Primary endpoints for this study included overall survival in patients with PD-L1 tumor proportion scores of ≥50%, ≥20%, and ≥1%. Secondary endpoints were progression-free survival and overall response rate as well as a review of drug safety.

A total of 1,274 patients were randomized to either pembrolizumab or chemotherapy with 637 patients in each treatment arm. Overall survival was higher in the pembrolizumab arm regardless of PD-L1 tumor proportion score. 

Grade 3-5 adverse events occurred in 18.9% of the pembrolizumab treatment arm and in 41.8% of the chemotherapy arm. 

For the 102 patients who completed the full 35 cycles of pembrolizumab, there was an overall response rate of 84.3%. The 4-year estimated overall survival was 61.8%. 

Due to the initial data from KEYNOTE-042 coupled with the 5-year follow-up data, first-line pembrolizumab therapy remains the standard of care in patients with PD-L1 expressing non-small-cell lung cancer.