Cemiplimab Plus Chemotherapy Provides Long-Term Survival Benefit in Advanced NSCLC

Cemiplimab (Libtayo) plus chemotherapy demonstrated sustained survival benefits in patients with advanced non–small cell lung cancer (NSCLC), according to 5-year follow-up findings from the phase 3 EMPOWER-Lung 3 Part 2 trial (NCT03409614) presented at the International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer.1

At a median follow-up of 60.9 months (range, 53.0-68.4), patients who received cemiplimab plus chemotherapy (n = 312) achieved a median overall survival (OS) of 21.1 months (95% CI, 15.9-23.9) compared with 12.9 months (95% CI, 10.6-16.1) in the placebo plus chemotherapy arm (n = 154), translating to a 34% reduction in the risk of death (HR, 0.662; 95% CI, 0.531-0.825; P = .0002). The median progression-free survival (PFS) with cemiplimab was 8.2 months (95% CI, 6.5-9.0) vs 5.5 months (95% CI, 4.3-6.2) without it (HR, 0.579; 95% CI, 0.467-0.718; P < .0001).

The objective response rate (ORR) was 43.6%, including a complete response (CR) rate of 6.4% and partial response (PR) rate of 37.2%; the ORR in the placebo arm was 22.1%, which consisted entirely of PRs (odds ratio, 2.82; 95% CI, 1.80-4.42; P < .0001). The median duration of response (DOR) was 16.4 months (95% CI, 13.1-19.5) with cemiplimab plus chemotherapy vs 7.3 months (95% CI, 4.2-11.3) with placebo plus chemotherapy.

“At 5-year follow-up, the EMPOWER-Lung 3 trial continues to show durable long-term survival benefits with the use of cemiplimab plus chemotherapy compared to chemotherapy as first-line therapy for advanced NSCLC,” Ana Baramidze, MD, Head of the Department of Clinical Researches at Todua Clinic in Tblisi, Georgia. “Long-term survival benefit was observed regardless of histology.”

What Did the EMPOWER-Lung 3 Part 2 Study Examine?

EMPOWER-Lung 3 Part 2 (NCT03409614) was a global, randomized, double-blind, phase 3 study that evaluated cemiplimab in combination with chemotherapy vs chemotherapy alone in patients with advanced NSCLC.2 Patients were randomized in a 2:1 ratio to receive cemiplimab 350 mg every 3 weeks (Q3W) plus platinum-doublet chemotherapy for 4 cycles or placebo Q3W plus investigator’s choice of platinum-doublet chemotherapy for 4 cycles Q3W. Treatment continued until progressive disease or a maximum of 108 weeks.

Eligible patients were required to have treatment-naive, advanced nonsquamous or squamous NSCLC (stage IIIB/C or IV) and any level of PD-L1 expression.1,2 They had an ECOG performance status of 0 or 1 and no known EGFR, ALK, or ROS1 alterations. Individuals with treated, clinically stable central nervous system metastases were permitted to enroll. Stratification factors included PD-L1 expression (<1% vs 1%-49% vs ≥50%) and histology (nonsquamous vs squamous).

The trial’s primary end point was OS. Key secondary end points included PFS and ORR, with additional secondary end points of DOR and safety.

What Additional Efficacy Data Were Reported With Cemiplimab Plus Chemotherapy?

The 12-, 24-, 36-, and 60-month OS rates with cemiplimab plus chemotherapy were 66.4%, 43.9%, 33.2%, and 19.4%, respectively; with chemotherapy alone, these respective rates were 53.9%, 27.7%, 17.9%, and 8.8%. It was noted that the 5-year data were consistent with prior reports at 1 year, where the median OS with cemiplimab was 21.9 months vs 13.0 months without (HR, 0.71), and at 2 years, where the median OS was 21.1 months vs 12.9 months (HR, 0.65). Additionally, the 12-, 24-, 36-, and 60-month PFS rates with cemiplimab plus chemotherapy were 38.4%, 20.1%, 17.3%, and 8.8%, respectively; with chemotherapy alone, these rates were 17.2%, 5.7%, 5.7%, and 0%, respectively.

In those with squamous histology, the median OS was 22.3 months (95% CI, 15.7-27.2) with cemiplimab plus chemotherapy vs 13.8 months (95% CI, 9.3-18.0) with chemotherapy alone (HR, 0.678; 95% CI, 0.488-0.941). The OS rates at 12, 24, 36, and 60 months in the cemiplimab combination arm were 70.6%, 46.1%, 33.9%, and 18.0%, respectively; in the chemotherapy-alone arm, these respective rates were 57.0%, 31.9%, 21.8%, and 10.1%. In those with nonsquamous histology, the median OS with cemiplimab plus chemotherapy led to a median OS of 19.4 months (95% CI, 14.0-24.0) vs 12.4 months (95% CI, 10.1-16.1) with chemotherapy alone (HR, 0.615; 95% CI, 0.460-0.822). In the cemiplimab arm, the OS rates at 12, 24, 36, and 60 months were 63.2%, 42.3%, 32.7%, and 20.4%, respectively; in the chemotherapy-alone arm, these rates were 51.5%, 24.4%, 14.9%, and 8.1%.

Moreover, in patients with a PD-L1 expression of 1% or higher, the median OS with cemiplimab plus chemotherapy (n = 217) was 24.0 months (95% CI, 20.9-28.4) vs 12.1 months (95% CI, 10.1-15.7) with chemotherapy alone (n = 110; HR, 0.537; 95% CI, 0.41-0.70; P < .0001). The 12-, 24-, 36-, and 60-month OS rates with cemiplimab were 72.4%, 49.8%, 38.7%, and 23.5%, respectively; without it, these rates were 51.0%, 28.8%, 19.2%, and 8.2%. The median PFS in the respective arms was 8.3 months (95% CI, 6.7-10.8) vs 5.5 months (95% CI, 4.3-6.2; HR, 0.505; 95% CI, 0.390-0.653). Additionally, cemiplimab plus chemotherapy elicited an ORR of 48.4% (95% CI, 41.6%-55.2%) vs 22.7% (95% CI, 15.3%-31.7%) with chemotherapy alone (odds ratio, 3.185; 95% CI, 1.895-5.355); the median DOR in the respective arms was 18.2 months (95% CI, 13.3-21.5) and 6.5 months (95% CI, 4.2-10.3; HR, 0.428; 95% CI, 0.247-0.741).

Lastly, 21.2% of the 312 patients in the cemiplimab/chemotherapy arm completed 2 years of cemiplimab treatment per trial protocol, and in these patients, the 60-month OS rate was 56.0%.

What Were the Long-Term Safety Outcomes With Cemiplimab Plus Chemotherapy?

At the data cutoff date of February 27, 2025, the median duration of exposure was 38.8 weeks (range, 1.4-130.0) in the cemiplimab arm (n = 312) compared with 21.3 weeks (range, 0.6-140.3) in the placebo plus chemotherapy arm (n = 153).

Treatment-emergent adverse effects (TEAEs) of any grade were reported in 96.5% of patients who received cemiplimab plus chemotherapy vs 94.8% of those in the placebo arm. Grade 3 or higher TEAEs occurred in 49.4% and 32.7% of patients, respectively. Long-term safety outcomes with cemiplimab plus chemotherapy were consistent with previously reported data.

Disclosures: No disclosures were listed for Baramidze.

References

1. Baramidze A, Makharadze T, Gogishvili M, et al. Cemiplimab plus chemotherapy vs chemotherapy in advanced NSCLC: 5-year results from phase 3 EMPOWER-Lung 3 Part 2 trial. Presented at: 2025 IASLC World Conference on Lung Cancer; September 6-10,2025; Barcelona, Spain. Oral presentation MA10.09.
2. Combinations of cemiplimab (anti-PD-1 antibody) and platinum-based doublet chemotherapy in patients with lung cancer. Clinialtrials.gov. Updated March 13, 2025. Accessed September 9, 2025. https://clinicaltrials.gov/study/NCT03409614