Recently, the FDA granted approval to cemiplimab-rwlc (Libtayo®, Regeneron Pharmaceuticals, Inc.) for the first-line treatment of patients with advanced non-small lung cancer cell (NSCLC) whose tumors express programmed death ligand 1 (PD-L1) in at least 50% of their cells and whose tumors do not have aberrations in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or C-ROS oncogene 1 (ROS1). In this interview, Ahmet Sezer, MD, Professor in the Department of Medical Oncology at Başkent University in Adana, Turkey, and principal investigator for the phase 3 EMPOWER-Lung 1 trial (NCT03088540), on which the approval was based, speaks with Oncology Data Advisor about the challenges of treating patients with advanced NSCLC and cemiplimab's potential as a treatment option.
Can you comment on the significance of the FDA's approval of cemiplimab for the first-line treatment of advanced NSCLC?
Dr. Sezer: In advanced NSCLC, PD-1 inhibitors have become a key component of systemic treatment in patients with advanced NSCLC without EGFR, ALK or ROS1 mutations. However, there is still a need to optimize chemotherapy-free treatment options for patients with high PD-L1 expression levels.
In its phase 3 trial, known as EMPOWER-Lung 1, cemiplimab demonstrated an impressive level of efficacy compared to chemotherapy and was superior in extending overall survival. This was achieved with a greater than 70% crossover rate to cemiplimab following disease progression on chemotherapy and reinforces the potential of cemiplimab as a valuable treatment option for appropriate patients with advanced NSCLC with PD-L1 expression of at least 50%.
In addition, EMPOWER-Lung 1 enrolled patients with disease characteristics frequently underrepresented in advanced NSCLC trials. Among these patients, 12% had pretreated and clinically stable brain metastases, and 16% had locally advanced NSCLC that left them ineligible for definitive chemoradiation. As a result, the medical community now has valuable new clinical evidence that could enhance our understanding of how to treat advanced NSCLC.
How does cemiplimab compare with other first-line treatments for NSCLC?
Dr. Sezer: As published in The Lancet, in a prespecified analysis in the subset of patients proven to have PD-L1 expression of at least 50%, cemiplimab reduced the risk of death by 43% compared to chemotherapy. There are no head-to-head studies comparing cemiplimab and any other PD-1 inhibitors in advanced NSCLC, so it's difficult to make any comparative conclusions around efficacy or safety here.
However, the EMPOWER-Lung 1 trial was notable in that it explored cemiplimab monotherapy in a large population that allowed for disease characteristics frequently underrepresented in pivotal advanced NSCLC clinical trials.
How do you see the treatment of NSCLC evolving? What research advances are on the horizon?
Dr. Sezer: There is still a lot we don't know about advanced NSCLC, and more research is always needed to further enhance patient outcomes for this deadly disease. Thankfully, we've seen clinical research in advanced NSCLC continue to grow significantly. I believe EMPOWER-Lung 1 is an important step and offers physicians valuable new data that can help them in treating the varied patients and situations they come across in daily clinical practice.
For cemiplimab specifically, this PD-1 inhibitor is currently being studied in combination with chemotherapy in a Phase 3 trial in patients with advanced NSCLC irrespective of PD-L1 expression. That trial is now fully enrolled, and initial data is expected later this year. I'm looking forward to seeing the results.
Do you have any words of advice for community pulmonologists and oncologists treating patients with advanced NSCLC?
Dr. Sezer: There is no "one size fits all" approach for treating a complex disease like advanced NSCLC, so it is always important to consider each individual patient and his or her particular needs. The physicians who treat advanced NSCLC––myself included––are a data-driven group who appreciate having multiple treatment options, so I encourage the medical community to continue to evaluate new data and therapies when making treatment decisions. I personally find it encouraging to see trials like EMPOWER-Lung 1 being conducted in patient populations with a variety of disease characteristics, different countries, and different treatment sequences. Collectively, all of this ongoing research is helping us refine how we understand and treat advanced NSCLC.
About Dr. Sezer
Ahmet Sezer, MD, is a Professor in the Department of Medical Oncology at Başkent University in Adana, Turkey. He specializes in the treatment of patients with lung cancer, including NSCLC. Dr Sezer is a member of the American Society of Clinical Oncology and the European Society of Medical Oncology. Dr. Sezer serves as principal investigator or co-investigator of several global clinical trials focusing on the development of novel therapeutics for patients with lung cancer, and he has authored or coauthored numerous publications in peer-reviewed journals.
For More Information
Sezer A, Kilickap S, Gümüş M, et al (2021). Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Lancet, 397(10274):592-604. DOI:10.1016/S0140-6736(21)00228-2
Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of Oncology Data Advisor.