Cemiplimab Makes Case as First-Line, Nonchemotherapy Treatment in Metastatic NSCLC

After 3 years of follow-up, findings from the EMPOWER-Lung1 trial (NCT03088540) demonstrated further improvement in overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) in patients with advanced or metastatic non–small cell lung cancer. Patients were given cemiplimab-rwlc (Libtayo) vs chemotherapy and continued to see improvements in OS despite a crossover rate of 75%, according to data presented by Mustafa Özgüroğlu, MD, during the International Association for the Study of Lung Cancer 2022 North America Conference on Lung Cancer.¹

In the second part of the trial, patients were allowed to continue cemiplimab therapy with the addition of histologic-specific chemotherapy beyond progression; this resulted in durable responses and an ORR of 31.3%. In patients with PD-L1 greater than or equal to 50%, patients in the cemiplimab arm had a median OS of 26.1 months (95% CI, 22.1-31.8) vs 13.3 months in the chemotherapy arm (95% CI, 10.5-16.2) Risk of death was 43% (HR, 0.57; 95% CI, 0.46-0.71; P < .0001).

Similarly, PFS rates favored patients in the cemiplimab arm. Median PFS was 8.1 months in the treatment arm (95% CI, 6.2- 8.8) vs 5.3 months in the control arm (95% CI, 4.3-6.1). Risk of progression was 49% (HR, 0.51; 95% CI, 0.42-0.62; P < .0001).

ORR and duration of response also favored cemiplimab over chemotherapy with patients treated with cemiplimab with an ORR of 46.5% vs 21.0% in patients treated with chemotherapy (OR, 3.26; P < .0001).

Investigators reported that median duration of response (DOR) was reported as 23.6 months in the cemiplimab arm vs 5.9 months in the chemotherapy arm. Complete response (CR) was 8.1% (n = 284) in the cemiplimab arm compared with 2.1% (n = 281) in the treatment arm.

“The effect of PD-L1 levels was interesting,” said Özgüroğlu, professor of medical oncology, Istanbul University, Turkey. “Increases in ORR in patients given cemiplimab correlated with PD-L1 expression levels,” he continued.

In patients with PD-L1 greater than or equal to 90%, ORR for patients who received cemiplimab (n = 99) was 60.6% vs 17.9% in patients who received chemotherapy (n = 95). For patients with PD-L1 levels between 60% and 90%, those who received cemiplimab (n = 89) had an ORR of 43.8% vs 22.2% for those who received chemotherapy (n = 90). For PD-L1 levels between 50% and 60%, ORR was 34.4% for those who received cemiplimab (n = 96) vs 22.9% for those who received chemotherapy (n = 96). Özgüroğlu reported similar findings for PFS rates and PD-L1 levels (TABLE¹).

In the EMPOWER-Lung 1 trial, 721 patients in the intent-to-treat population were randomly assigned to receive 350 mg of cemiplimab every 3 weeks (arm A) vs 4 to 6 cycles of investigator’s choice for chemotherapy (arm B).

Eligible patients had treatment-naïve advanced NSCLC with PD-L1 levels greater than or equal to 50%, with an ECOG performance status of 0 or 1. The primary end points were OS and PFS, and secondary end points were ORR, DOR, and safety. At disease progression, patients in arm A could continue cemiplimab plus 4 cycles of chemotherapy. At disease progression, patients in arm B could cross over to receive cemiplimab monotherapy. A total of 565 patients had PD-L1 greater than or equal to 50% as determined by 22C3 assay.

In patients with PD-L1 greater than or equal to 50%, baseline characteristics were similar between the 2 arms. Median age was 63 years in the cemiplimab arm (n = 284) and 64.0 years in the chemotherapy arm (n = 281). The majority of patients for both arms were male (87.7% vs 82.2%, respectively).

“Safety profiles were consistent with previous studies involving cemiplimab,” noted Özgüroğlu. Any grade treatment-related adverse events (AEs) in the cemiplimab arm was 62.6% and discontinuation occurred in 7.3% in the treatment arm. Any grade treatment-emergent AEs were anemia (19.7%), decreased appetite (14.3%), and fatigue (13.8%). The most common grade 3-5 AEs were pneumonia (5.3%), anemia (4.2%), and dyspnea (2.8%).

After initial treatment with cemiplimab and disease progression, patients were given 4 cycles of chemotherapy (n = 64). After progression, Özgüroğlu said 3 patients had a complete response, 17 had a partial response, 35 patients had stable disease, and 9 patients progressed.

Improved PFS was reported after the addition of chemotherapy: at 6 months, the PFS rate was 50.7% in patients who received the initial monotherapy vs 66.2% after chemotherapy was added. Similarly, at 12 months, PFS was 24.1% vs 31.2%; at 18 months, 0.0% vs 15.7%; and at 24 months, 0.0% vs 8.4%, respectively.

“Overall, these results support the use of cemiplimab as a first-line, chemotherapyfree treatment for patients with advanced or metastatic NSCLC and PD-L1 greater than or equal to 50%,” Özgüroğlu concluded.

REFERENCE

1. Özgüroğlu M. Three-year outcomes per PD-L1 status and continued cemiplimab beyond progression + chemotherapy: EMPOWER-Lung 1. Presented at: 2022 North American Conference on Lung Cancer; September 23-25, 2022; Chicago, IL. Accessed October 11, 2022. Abstract OA01.05. https://bit.ly/3ECVmmy