Cemiplimab/Chemo Represents New Frontline Option for Advanced NSCLC Without Actionable Mutations

Cemiplimab-rwlc (Libtayo) plus platinum-doublet chemotherapy significantly improved outcomes when used in the frontline treatment of patients with advanced non–small cell lung cancer (NSCLC) compared with chemotherapy alone, according to Miranda Gogishvili, MD, who added that benefits were observed with the immunotherapy, even in difficult-to-treat subsets with diverse disease characteristics and varying levels of PD-L1 expression.

In the phase 3 EMPOWER-Lung 3 trial (NCT03409614), those who received cemiplimab plus chemotherapy (n = 312) experienced a significant improvement in overall survival (OS) vs those who were given chemotherapy alone (n = 154), at 21.9 months (95% CI, 15.5–not evaluable) vs 13.0 months (95% CI, 11.9-16.1), respectively (HR, 0.71; 95% CI, 0.53-0.93; P = .014).¹

Cemiplimab was also associated with superior median progression-free survival of 8.2 months (95% CI, 6.4-9.3) vs 5.0 months (95% CI, 4.3-6.2) in the placebo arm (HR, 0.56; 95% CI, 0.44-0.70; P < .0001). Moreover, the addition of the immunotherapy to chemotherapy resulted in a higher objective response rate (ORR) than chemotherapy alone, at 43.3% (95% CI, 37.7% vs 49.0%) and 22.7% (95% CI, 16.4%-30.2%), respectively (odds ratio, 2.68; 95% CI, 1.72-4.19; P < .0001).

“EMPOWER-Lung 3 demonstrated that cemiplimab in combination with chemotherapy can significantly extend survival in patients with locally advanced or metastatic NSCLC across different PD-L1 expression levels in both squamous and nonsquamous histologies,” Gogishvili said. “Furthermore, these clinically meaningful benefits were achieved in a trial that enrolled patients with baseline characteristics commonly considered to be difficult to treat. The cemiplimab combination also demonstrated favorable patient-reported outcomes [PROs].”

In an interview with OncLive®, Gogishvili, medical oncologist at the High Technology Medical Center, University Clinic, discusses the rationale for examining cemiplimab plus platinum-doublet chemotherapy as a frontline treatment in patients with advanced NSCLC and key findings from the phase 3 EMPOWER-Lung 3 trial.

OncLive®: What was the rationale for conducting the EMPOWER-Lung 3 trial?

Gogishvili: Cemiplimab was approved earlier this year in both the United States and Europe. In Europe, the immunotherapy is a first-line treatment for patients with advanced NSCLC and a PD-L1 expression of 50% or greater based on results from the EMPOWER-Lung 1 trial [NCT03088540].

With EMPOWER-Lung 3, we set out to explore the combination of cemiplimab with platinum-doublet chemotherapy, which led to positive outcomes in patients with squamous and nonsquamous histologies, diverse disease characteristics seen in everyday clinical practice, and different levels of PD-L1 expression.

What is the importance of these findings taken in conjunction with EMPOWER-Lung 1?

The study met its primary OS end point and all key secondary end points and [the addition of cemiplimab resulted in a] significant improvement in OS compared with chemotherapy alone. The median OS was [approximately] 22.0 months with the cemiplimab combination compared with 13.0 months for chemotherapy.

The median PFS was [about] 8.0 months with the cemiplimab combination compared with 5.0 months for chemotherapy. The objective response rate was [approximately] 43% with cemiplimab combination vs [about] 23% for chemotherapy. Moreover, the median duration of response was [almost] 16.0 months with cemiplimab combination compared with [about] 7 months for chemotherapy.

Favorable [PROs] were also observed [with cemiplimab]. Specifically, the combination delayed deterioration and pain symptoms and showed a trend toward delaying deterioration in Global Health Status/quality of life compared with chemotherapy. The cemiplimab combination also improved pain symptoms vs chemotherapy alone.

What was the safety profile of the combination?

No new safety signals for cemiplimab were identified. Adverse effects [AEs] of any grade occurred in 96% of patients receiving the combination and 94% of those receiving chemotherapy alone; immune-related effects were reported in 19% and 0% [of patients], respectively.

In the cemiplimab combination and chemotherapy groups, the most common AEs were anemia, alopecia, and nausea. Grade 3 or higher AEs that occurred in more than 5% of patients were anemia and neutropenia. Treatment discontinuation due to AEs occurred in 5% of patients receiving cemiplimab/chemotherapy and 3% receiving chemotherapy alone.

What is the take-home message regarding this research?

These results add to the growing body of evidence supporting the use of cemiplimab as a component of treatment in patients with advanced NSCLC across multiple clinical settings.

Reference

1. Gogishvili M, Melkadze T, Makharadze T, et al. EMPOWER-Lung 3: cemiplimab in combination with platinum-doublet chemotherapy (chemo) for first-line (1L) treatment of advanced non-small cell lung cancer (NSCLC). Presented at: 2021 ESMO Congress; September 19, 2021; Virtual. https://bit.ly/3mmTt2A