Cemiplimab improves 5-year survival in advanced NSCLC with PD-L1 expression ≥50 percent

First-line cemiplimab monotherapy continues to provide durable overall (OS) and progression-free survival (PFS) benefits at 5 years compared with chemotherapy in advanced nonsmall cell lung cancer (NSCLC) patients with PD-L1 expression ≥50 percent, according to the results of the EMPOWER-Lung 1 study presented at WCLC 2024.

The clinical benefits from cemiplimab increase with PD-L1 expression levels, and those with PD-L1 ≥90 percent gain the largest benefits.

“These results increase our understanding of potential treatment strategy beyond progression for patients receiving first-line cemiplimab monotherapy for advanced metastatic NSCLC with PD-L1 ≥50 percent,” said co-author Dr Ana Baradmize from Todua Medical Center, Tbilisi, Georgia.

In the EMPOWER-Lung 1, a multicentre, open-label, randomized phase III study, Baradmize and her team randomly assigned 712 patients with treatment-naïve squamous or nonsquamous NSCLC to receive cemiplimab 350 mg IV (n=357) every 3 weeks for 2 years or chemotherapy (n=355). Of these, 565 (284 in the cemiplimab arm and 281 in the chemotherapy arm) had confirmed PD-L1 ≥50 percent.

Baradmize and colleagues also conducted a postprogression analysis on patients who received a single dose of chemotherapy and at least one scan following disease progression on cemiplimab. A blinded independent review committee evaluated the response against a new baseline, defined as the last scan before the initial chemotherapy dose.

Clinical benefits

The median OS over a median follow-up of 57.3 months was 26.1 months (95 percent confidence interval [CI], 22.1‒31.9) for cemiplimab versus 13.3 months (95 percent CI, 10.5‒16.2) for chemotherapy (hazard ratio [HR], 0.585, 95 percent CI, 0.48‒0.72). [WCLC 2024, abstract OA11.06]

Additionally, the median PFS was 8.1 months (95 percent CI, 6.2‒8.8) for cemiplimab versus 5.3 months (95 percent CI, 4.3‒6.1) for chemotherapy (HR, 0.500, 95 percent CI, 0.41‒0.61), while the objective response rate (ORR) was 46.5 percent (95 percent CI, 40.6‒52.5) versus 20.6 percent (95 percent CI, 16.1‒25.8), respectively.

At 5 years, the OS probability was 29.0 percent (95 percent CI, 22.9‒35.4) in the cemiplimab arm compared with 15.0 percent (95 percent CI, 10.5‒20.2) in the chemotherapy arm.

Notably, patients with PD-L1 ≥90 percent derived the largest clinical benefit with cemiplimab, with a median OS of 38.8 months (95 percent CI, 22.9‒NE), median PFS of 14.7 months (95 percent CI, 10.2‒21.1), ORR of 60.6 percent (95 percent CI, 50.3‒70.3), and 5-year OS probability of 39.8 percent (95 percent CI, 28.0‒51.3).

In terms of safety at 5 years, both interventions showed a consistent profile when compared with previous results. Grade 3 or higher treatment-emergent adverse events occurred in 45.8 percent of cemiplimab-treated patients and 51.6 percent of those who received chemotherapy.

In the postprogression analysis involving 75 patients treated with cemiplimab plus chemotherapy, the median PFS was 6.5 months (95 percent CI, 6.2‒8.3) and the ORR was 28.0 percent (95 percent CI, 18.2‒39.6). The median OS from randomization was 27.4 months (95 percent CI, 23.0‒31.9), which included a median of 15.1 months (95 percent CI, 11.3‒18.0) after adding chemotherapy.

The combination treatment was generally well tolerated, and only 27 patients (36.0 percent) developed grade ≥3 TEAEs during the postprogression phase.

“Continued cemiplimab beyond progression with the addition of chemotherapy demonstrates meaningful clinical benefits, providing a potential new treatment option for patients who progressed on first-line cemiplimab monotherapy,” Baradmize said.