Long-Term Data Confirms Cemiplimab Benefits in High PD-L1 NSCLC

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EMPOWER-Lung (NCT03409614) is a phase 3 clinical trial evaluating the efficacy and safety of the immune checkpoint inhibitor cemiplimab (Libtayo) compared with chemotherapy for treating advanced non–small cell lung cancer (NSCLC). The study focused on patients with PD-L1 expression levels of at least 50% and no other specific genetic alterations.

Here, cemiplimab demonstrated a significant survival advantage over chemotherapy. Patients treated with cemiplimab had a longer median overall survival of 26.1 months compared with 13.3 months for those treated with chemotherapy. Cemiplimab also showed a higher objective response rate of 46.5% and progression-free survival of 8.1 months compared with chemotherapy. Further, the safety profile of cemiplimab was generally acceptable.

In patients who progressed on cemiplimab monotherapy, adding chemotherapy as a second-line treatment provided additional benefits. Overall, these results suggest that cemiplimab is a promising treatment option for patients with NSCLC and high PD-L1 expression.

Here, Ana Baramidze, MD, PhD, Todua Clinic, Tbilisi, Georgia, discusses a 5-year follow-up of the study, its findings, and implications.

Targeted Oncology: Can you provide some background to the study?

Ana Baramidze, MD, PhD

Baramidze: The EMPOWER-Lung study was a randomized phase 3 trial designed to assess clinical benefit of cemiplimab monotherapy in newly diagnosed patients with advanced non–small cell lung cancer with PD-L1expression in 50% or more of tumor cells and no EGFR, ALK, or ROS1 aberrations. Theprimary end points were overall survival and progression-free survival.

An innovative feature of this study allowed for patients who experienced disease progression to change the therapy, and the patients randomized to chemotherapy were allowed to cross over to cemiplimab, and this crossover occurred in 75% of patients who progressed on chemotherapy. Those randomized to cemiplimab were allowed optional continuation of cemiplimab but with the addition of the chemotherapy,

Could you compare what were the initial findings and how they compare to the 5-year follow-up?

The 5-year results confirm durable survival benefit across multiple efficacy points of cemiplimab vs chemotherapy. In this setting, additional patients whose disease progressed on cemiplimab saw a clinically meaningful benefit when chemotherapy was added to their treatment regimen.

An exploratory subgroup analysis of cemiplimab-treated patients also show the direct correlation between survival and disease progression benefits and PD-L1ne expression level. Notably, the patients with PD-L1 expression level 90% and more derive the greatest clinical benefit with 39 months median overall survival and 15 months median progression free survival. This support the direct correlation between tumor response and PD-L1 expression level previously observed with cemiplimab.

The safety profile of the cemiplimab at 5 years of follow-up was consistent with that report in previous analysis,

Based on these longer-term findings, what would you consider to be the major implications for physicians?

Long-term follow-up in cancer is always an important measure to examine and is especially critical for newly diagnosed patients with advanced non–small cell lung cancer, and these results increase our understanding of potential treatment strategy beyond progression for patients receiving first-line cemiplimab monotherapy for advanced non–small cell lung cancer. Additionally, to the best of our knowledge, this is the first to show in prospective studies, through an exploratory analysis, that the benefit of cemiplimab is highest in patients was at least 90% of PD-L1 expression and provided strong support for the use of first line anti PD-1 agents as monotherapy in this patient population.

For this patient population, what do you consider to still be some of the unmet needs?

Lung cancer is the most commonly diagnosed cancer globally, accounting for an estimated 2.4 million cases annually. It’s also the leading cause of cancer deaths with1.5 million deaths, or 1 in 5 in 2022. Despite significant advancements due to improving the prevention or detection and treatment of advanced non–small cell lung cancer in the recent years, the high prevalence of disease and mortality rate variants warrant further research to help tailor treatment approaches to each individual patient.

REFERENCE:
Kilickap S, Sezer A, M. Özgüroğlu, et al. Cemiplimab monotherapy for first line advanced NSCLC patients with PD-L1 expression ≥50%: 5-y outcomes of EMPOWER-Lung. Presented at: IASLC 2024 World Conference on Lung Cancer; September 7-10, 2024; San Diego, CA. Abstract OA 11.06.