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Frontline Cemiplimab With Chemo Offers Benefits in Advanced NSCLC Regardless of PD-L1 Status


Sanofi and Regeneron had previously announced an overall survival advantage of 29% over chemotherapy alone; the combination also had a progression-free survival benefit of 46%.

Cemiplimab, approved as a first-line monotherapy to treat patients with advanced or metastatic non-small cell lung cancer (NSCLC) and high levels of PD-L1, offered benefits to patients regardless of PD-L1 status when given with a platinum-based chemotherapy doublet in the same setting, according to new findings.

Interim results from the EMPOWER-Lung 3 study1 were presented September 19 during the European Society of Medical Oncology (ESMO) 2021 Virtual Congress, by trial investigator Miranda Gogishvili, MD, oncologist at the High Technology Medical Center University Clinic, in Tbilisi, Georgia.

“Cemiplimab in combination with platinum-doublet chemotherapy is a new first-line treatment option for patients in advanced NSCLC without targetable mutations irrespective of histology and PD-L1 levels,” she concluded.

Gogishvili noted a previously announced finding that patients taking cemiplimab saw a 29% relative reduction in the risk of death (overall survival) compared with those taking chemotherapy alone; she also highlighted a 46% relative reduction in the risk of disease progression (progression-free survival) compared with those taking chemotherapy.

The 12-month probability of survival was 66% for those taking the cemiplimab combination vs 56% for the chemotherapy.

In announcing topline results in August, officials from Regeneron and Sanofi, who market the immunotherapy as Libtayo, said that independent monitors had called for ending EMPOWER-Lung 3 early due to results seen during a protocol-specific interim analysis.2

Based on earlier findings in the EMPOWER-Lung 1 trial,3 cemiplimab received FDA approval in February 2021 as a first-line therapy in advanced NSCLC for patients with ≥50% PD-L1 expression.4 The EMPOWER-Lung 3 study studied patients with squamous and nonsquamous advanced NSCLC, irrespective of PD-L1 expression. These patients screened negative for ALKEGFR, and ROS1 mutations, had not been treated for metastatic or locally advanced disease, and were not eligible for chemoradiation.5

The 466 patients in the trial were randomized 2:1 to receive the cemiplimab combination or a chemotherapy doublet. At the time of enrollment, 30% had tumors with <1% PD-L1 expression, 38% had tumors with 1% to 49% PD-L1 expression, and 33% of patients had tumors with ≥50% PD-L1 expression. Details of the findings showed:

  • The median age of the patients was 63.0 years; 57.1% had non-squamous NSCLC, and 85.2% had stage IV disease.
  • Median OS was 21.9 months with cemiplimab plus chemotherapy, compared with 13.0 months for chemotherapy and placebo, for a hazard ratio (HR) of 0.71 (95% CI, 0.53-0.93; P = .014).
  • Median PFS was 8.2 months with cemiplimab plus chemotherapy vs 5.0 months for chemotherapy and placebo, for HR of 0.56 (95% CI: 0.44 to 0.70; P < .0001).
  • Cemiplimab with chemotherapy had a higher objective response rate (43.3% vs 22.7%), and longer duration of response (15.6 months vs 7.3 months) than chemotherapy and placebo.
  • Adverse events of grade 3 or higher were more common in the cemiplimab arm, 43.6% vs 31.4% in the chemotherapy and placebo arm.
  • By PD-L1 status, patients ≥50% had HR 0.61 in OS and 0.47 in PFS, both favoring cemiplimab; patients 1%-49% had HR 0.52 in OS and 0.47 in PFS, both favoring cemiplimab; patients <1% had HR 0.76 in PFS favoring cemiplimab and 1.01 in OS, not favoring either arm.
  • Most subgroups favored cemiplimab, with the exception of never smokers and women, but both groups had low overall enrollment in the trial. Of the 466 patients, 75 were women and 67 were never smokers.

Lung cancer is the leading cause of cancer death in both the United States and worldwide. Last year, an estimated 225,000 new cases were diagnosed in the United States, and most are diagnosed at later stages when cancer is hard to treat. In response, the US Preventive Services Task Force recently adopted new screening guidelines to diagnose more people with lung cancer at earlier stages.6

According to a statement from Sanofi and Regeneron, approximately 70% of all new NSCLC cases will have <50% PD-L1 expression, making it the most common treatment setting, so the latest results could affect most patients diagnosed with this disease.7

“This phase 3 trial was stopped early because Libtayo significantly improved overall survival compared to chemotherapy, a milestone also achieved by our phase 3 for Libtayo monotherapy as a first-line treatment for advanced non-small cell lung cancer with high PD-L1 expression,” Israel Lowy, MD, PhD, senior vice president for Translational and Clinical Sciences, Oncology at Regeneron, said in the statement.

“Both trials were designed to reflect everyday clinical practice by allowing for the enrollment of patients with difficult-to-treat disease characteristics,” he said. “This is the second Libtayo trial to demonstrate significant improvement in its primary and key secondary endpoints for these patient populations, compared to chemotherapy.”


  1. Gogishvili M, Melkadze T, Makharadze T, et al. EMPOWER-Lung 3: Cemiplimab in combination with platinum doublet chemotherapy for first-line (1L) treatment of advanced non-small cell lung cancer (NSCLC). Presented at: European Society of Medical Oncology 2021 Virtual Congress. Abstract LBA51.
  2. Phase 3 trial of Libtayo (cemiplimab-rwlc) combined with chemotherapy stopped early due to significant improvement in overall survival in patients with first-line advanced non-small cell lung cancer. News release. Regeneron Pharmaceuticals, Inc. August 5, 2021. Accessed September 19, 2021. https://bit.ly/3nL4DjV
  3. Sezer A, Kilickap S, Gumus 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, randomized, controlled trial. Lancet. 2021;397(10274):592-604. doi: 10.1016/S0140-6736(21)00228-2.
  4. FDA approves Libtayo (cemiplimab-rwlc) monotherapy for patients with first-line advanced non-small cell lung cancer with PD-L1 expression of ≥50%. News release. Regeneron Pharmaceuticals, Inc. February 22, 2021. Accessed September 19, 2021. https://investor.regeneron.com/index.php/news-releases/news-release-details/fda-approves-libtayor-cemiplimab-rwlc-monotherapy-patients-first
  5. Combinations of cemiplimab (anti-pd-1 antibody) and platinum-based doublet chemotherapy in patients with lung cancer. Clinicaltrials.gov. Accessed August 5, 2021. https://clinicaltrials.gov/ct2/show/NCT03409614
  6. Lung Cancer: Screening. US Preventive Services Task Force. Published March 9, 2021. Accessed September 19, 2021. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/lung-cancer-screening
  7. ESMO late-breaking data show Libtayo (cemiplimab) and chemotherapy first-line treatment combination significantly improved overall survival in patients with advanced NSCLC. News release. Published and accessed September 19, 2021. https://prn.to/3knFgCT
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