Cemiplimab Earns High Marks in First-Line Treatment of Advanced NSCLC

OncologyLive, Vol. 22/No. 19, Volume 22, Issue 19

Ahmet Sezer, MD, discusses how the approval of cemiplimab could potentially make a huge impact for patients with advanced non–small cell lung cancer.

On February 22, 2021, the FDA approved the PD-1 inhibitor cemiplimab-rwlc (Libtayo) for the first-line treatment of patients with advanced non–small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression (tumor proportion score > 50%) as determined by an FDA-approved test, with no EGFR, ALK, or ROS1 aberrations.1 Advanced disease was defined as patients who are not candidates for surgical resection, definitive chemoradiation, or who have metastatic disease.2

The approval was based on data from the phase 3 EMPOWER-Lung 1 trial (NCT03088540), which showed that patients treated with cemiplimab (n = 356) experienced an overall response rate (ORR) of 37% (95% CI, 32%-42%) compared with 21% (95% CI, 17%-25%) in patients treated with chemotherapy (n = 354). Notably, the median duration of response (DOR) was much higher in the cemiplimab cohort, registering at 21.0 months (1.9+ to 23.3+) compared with 6.0 months (1.3+ to 16.5+) for patients treated with chemotherapy. The median overall survival (OS) in the cemiplimab group was 22.1 months (95% CI, 17.7-not estimable) vs 14.3 months (95% CI, 11.7-19.2) in the chemotherapy group (HR, 0.68; 95% CI, 0.53-0.87; P = .0022).2

In an interview with OncLive®, Ahmet Sezer, MD, a professor in the Department of Medical Oncology at Başkent University in Ankara, Turkey, discussed how the approval of cemiplimab could potentially make a huge impact for patients with advanced NSCLC.

OncLive: What makes cemiplimab a novelty in the advanced NSCLC setting?

Cemiplimab is a fully humanized monoclonal antibody targeting the immune checkpoint receptor PD-L1 on T cells. Like other PD-1 inhibitors cemiplimab binds to PD-1 and has been shown to block cancer cells from using the pathway to suppress T-cell activation. In advanced NSCLC, PD-1 inhibitors have become a key component of the treatment of patients with advanced NSCLC without EGFR, ALK, or ROS1 mutations. However, there is still a need to optimize chemotherapy treatment options for patients with high PD-L1 expression levels.

In this pivotal phase 3 trial, EMPOWER-Lung 1, cemiplimab demonstrated an impressive level of efficacy and was superior in extending OS compared with chemotherapy. This 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, [investigators of] EMPOWER-Lung 1 enrolled more advanced patient populations, [which] are usually underrepresented in [other] advanced NSCLC trials. Among these patients, 12% [had] pretreated and stable brain metastases and 16% [had] locally advanced NSCLC [and were] not candidates for definitive chemotherapy radiation. As a result [of this protocol], the medical community now has valuable new clinical evidence that could enhance our understanding of how to treat advanced NSCLC.

Please elaborate on the efficacy and toxicity data that were observed in EMPOWER-Lung 1.

EMPOWER-Lung 1 compared first-line cemiplimab monotherapy with platinum-based chemotherapy in patients with advanced NSCLC with PD-L1 expression of at least 50%. The primary end points were OS and provision for survival. Secondary end points included ORR, DOR, and safety.

Cemiplimab demonstrated impressive efficacy early on and EMPOWER-Lung 1 was stopped early because of a highly significant improvement in OS compared with chemotherapy. Specifically, cemiplimab reduced the risk of death by 33% among all patients, and 43% in those with PD-L1 expression of at least 50%. These results were achieved with a greater than 50% crossover rate to cemiplimab following disease progression on chemotherapy. [Additionally, this is] the largest population of patients with pretreated and stable brain metastases among advanced NSCLC [included in a] pivotal trial to date.

To summarize, these results support cemiplimab as a new monotherapy option for patients with first-line advanced NSCLC with a PD-L1 expression of at least 50%. The safety profile of cemiplimab is consistent with the previous 2 reported profiles of the agent and other PD-L1 inhibitors in NSCLC and other tumor types.

Additional details have been published in The Lancet.3

How will this approval affect the treatment paradigm for patients with NSCLC with high PD-L1 expression?

Physicians, myself included, who treat [patients with] NSCLC are a data-driven group and appreciate having multiple treatment options. Given the impressive level of efficacy demonstrated in the EMPOWER-Lung 1 trial, I believe cemiplimab has the potential to make a meaningful difference for the many patients battling these difficult-to-treat cancers.

Additionally, [data from] EMPOWER-Lung 1 helps address current gaps in knowledge surrounding advanced NSCLC treatment, because it allows for certain patient and disease characteristics particularly underrepresented in [other] advanced NSCLC trials.

Are there any unanswered questions with the agent that future research should address?

We see many different patients with advanced NSCLC. Each patient is unique, and they can have a variety of disease characteristics that need to be considered. In short, there is still a lot we don’t know about advanced NSCLC treatment, and more research is always needed. However, I believe EMPOWER-Lung 1 is an important step and offers physicians valuable new data that can help them in treating various patients they come across in daily clinical practice.


  1. FDA approves cemiplimab-rwlc for non-small cell lung cancer with high PD-L1 expression. FDA. February 22, 2021. Accessed September 3, 2021. bit.ly/3tNGiLz
  2. Libtayo. Prescribing information. Regeneron Pharmaceuticals Inc; 2021. Accessed September 3, 2021. bit.ly/3hIBQZG
  3. Sezer A, Kilickap S, Gümüş M, et al. 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. 2021;397(10274):592-604. doi:10.1016/S01406736(21)00228-2