Frontline Cemiplimab Monotherapy Improved Overall, Progression-Free Survival for High PD-L1 NSCLC

Data published in The Lancet found that the PD-L1 inhibitor cemiplimab improved overall and progression-free survival for patients with advanced non–small cell lung cancer with PD-L1 of at least 50%.

First-line treatment with cemiplimab (Libtayo) monotherapy significantly improved overall survival (OS) and progression-free survival (PFS) when compared with chemotherapy for patients with advanced non–small cell lung cancer (NSCLC) and PD-L1 expression on at least 50% of cells, according to data published in The Lancet.1

The PD-L1 inhibitor monotherapy treatment was studied in the multicenter, open-label, global, randomized phase 3 EMPOWER-Lung-01 trial (NCT03088540), which supported the agent’s approval in February 2021 as a new treatment option for this patient population.2

“The results of EMPOWER-Lung-01 showed a clinically meaningful and statistically significant improvement in OS and PFS with first-line cemiplimab monotherapy over platinum-doublet chemotherapy in patients with advanced non–small cell lung cancer with PD-L1 of at least 50%, despite a high crossover rate and broadened inclusion criteria,” wrote the investigators.

Median OS was not reached (95% CI, 17.9-not evaluable) with cemiplimab (n = 283) compared with 14.2 months (11.2–17.5) with chemotherapy (n = 280; HR, 0.57; 95% CI, 0.42-0.77]; P = .0002) in the PD-L1 of at least 50% patient population.

More, in this same patient population, median PFS was recorded at 8.2 months (95% CI, 6.1-8.8) with cemiplimab treatment compared with 5.7 months (95% CI, 4.5-6.2) with chemotherapy (HR 0.54; 95% CI, 0.43-0.68; P <.0001).

Despite a crossover rate of 74% in the intention-to-treat population, the research team observed significant improvements in OS and PFS with cemiplimab.

In terms of the safety profile for the treatment options, grade 3 and 4 adverse events occurred in 98 (28%) of the 355 patients treated with cemiplimab and 135 (39%) of the 342 patients treated with chemotherapy.

“Of the approved PD-1 antibodies, only one, pembrolizumab [Keytruda], has shown survival benefit as monotherapy in this non–small cell lung cancer setting,” wrote the investigators. “These data provide a strong rationale for cemiplimab as a potential new treatment option for this patient population.”

The 710 patients included on the trial were randomly assigned between June 27, 2017 and February 27, 2020, with 563 patients included in the PD-L1 of at least 50% population.

The primary end points of the research were OS and PFS measured in the intention-to-treat population and in patients with a prespecified PD-L1 of at least 50%. The adverse event profile was also examined in all patients who received at least 1 dose of treatment.

“The study also included a proportion of patients with locally advanced non–small cell lung cancer who were not candidates for definitive chemoradiation, and those with treated and clinically stable brain metastases,” wrote the investigators. “These patients are usually under-represented in clinical trials, making the present study more reflective of real-world clinical practice.”


1. Sezer A, Kilickap S, Gumus M, et al. Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Lancet 2021; 397: 592–604.

2. FDA approves Libtayo (cemiplimab-rwlc) monotherapy for patients with first-line advanced non-small cell lung cancer with PD-L1 expression of ≥50%. News release. Regeneron Pharmaceuticals, Inc. February 22, 2021. Accessed February 26, 2021.