First-line therapy with pembrolizumab provides a long-term overall survival (OS) benefit over chemotherapy in patients with metastatic non-small cell lung cancer (NSCLC) and high PD-L1 expression, according to trial results published in the Journal of Clinical Oncology.

In the phase 3 KEYNOTE-024 trial ( Identifier: NCT02142738), investigators compared pembrolizumab with platinum-based chemotherapy in patients with previously untreated, metastatic NSCLC. Patients had a PD-L1 tumor proportion score (TPS) of at least 50% and did not have EGFR or ALK mutations.

The study enrolled 305 patients who were randomly assigned to receive pembrolizumab (154 patients) for 35 cycles or the investigator’s choice of chemotherapy (151 patients) for 4-6 cycles. Chemotherapy consisted of carboplatin plus paclitaxel or carboplatin/cisplatin plus pemetrexed or gemcitabine.

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In the chemotherapy group, 99 patients received subsequent anti-PD-1/PD-L1 therapy, which translates to a 66.0% crossover rate.

The final data cutoff was June 1, 2020, and the median follow-up was 59.9 months. The median duration of treatment was 7.9 months for the pembrolizumab arm and 3.5 months for the chemotherapy arm. 

The median OS was 26.3 months in the pembrolizumab arm and 13.4 months in the chemotherapy arm (hazard ratio, 0.62; 95% CI, 0.48-0.81). The 5-year OS rate was 31.9% and 16.3%, respectively.

There were 39 patients who completed 35 cycles of pembrolizumab, and 32 of them were still alive at last follow-up. At 36 months from treatment completion (roughly 5 years), their OS rate was 81.4%.

Longer treatment with pembrolizumab did not increase toxicity, and no new safety signals were identified. 

Treatment-related adverse events (TRAEs) occurred in 76.6% of patients in the pembrolizumab arm and 90.0% of patients in the chemotherapy arm. Grade 3-5 TRAEs occurred in 31.2% and 53.3%, respectively. Serious TRAEs were reported in 22.7% and 20.7%, respectively.

There were 2 treatment-related deaths in the pembrolizumab arm and 3 in the chemotherapy arm.

“In summary, these 5-year outcomes from the phase 3 KEYNOTE-024 study, which, to our knowledge, is the first randomized trial evaluating pembrolizumab in this setting,

show the ability of this treatment to improve long-term outcomes for patients with NSCLC,” the study authors wrote.

Based on these results, the authors suggested that pembrolizumab should be a standard therapy for patients with metastatic NSCLC and a PD-L1 TPS of at least 50%.

Disclosures: This research was supported by Merck Sharp & Dohme Corp. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Reck M, Rodríguez-Abreu D, Robinson AG, et al. Five-year outcomes with pembrolizumab versus chemotherapy for metastatic non-small-cell lung cancer with PD-L1 tumor proportion score ≥ 50%. J Clin Oncol. Published online April 19, 2021. doi: 10.1200/JCO.21.00174