European Commission Approves Cemiplimab Plus Chemotherapy for First-line PD-L1+ NSCLC

The European Commission has approved cemiplimab-rwlc (Libtayo) plus platinum-based chemotherapy for the frontline treatment of patients with locally advanced or metastatic PD-L1–positive non–small cell lung cancer (NSCLC) without EGFR, ALK, or ROS1 alterations and who are not eligible for chemoradiation.¹

The approval was based on findings from the phase 3 EMPOWER-Lung 3 trial, in which cemiplimab plus chemotherapy led to a statistically significant improvement in overall survival (OS) compared with chemotherapy alone (HR, 0.71; 95% CI, 0.53-0.93). In the PD-L1–positive population (n = 327; 70%), the median OS was 22 months with the combination vs 13 months with chemotherapy alone (HR, 0.55; 95% CI, 0.39-0.78).

“Today’s approval considerably expands the number of people in Europe with advanced non-small cell lung cancer who are eligible for [cemiplimab]-based first-line treatment, including those with PD-L1 expression ranges most commonly seen in real-world practice,” Israel Lowy, MD, PhD, senior vice president, Translational and Clinical Sciences, Oncology at Regeneron, said in a press release. “We are proud that [cemiplimab] continues to distinguish itself among PD-1 pathway blockers, as just one of two PD-1 inhibitors to be approved for use across squamous and non-squamous forms of advanced NSCLC in both combination and monotherapy settings. This marks the fifth approval for [cemiplimab] in Europe.”

EMPOWER-Lung 3 is a randomized, multicenter trial investigating the addition of cemiplimab to platinum-doublet chemotherapy vs platinum-doublet chemotherapy alone in the first-line setting. The trial enrolled 466 patients with locally advanced or metastatic NSCLC, irrespective of histology and PD-L1 expression. Patients were excluded if they had an EGFR, ALK, or ROS1 alteration. Among those enrolled, 43% had squamous histology, 15% had locally advanced disease, and 7% had a history of brain metastases.

Patients were randomly assigned 2:1 to receive 350 mg of cemiplimab (n = 312) or placebo (n = 154) administered intravenously every 3 weeks for 108 weeks, plus platinum-doublet chemotherapy administered every 3 weeks for 4 cycles. The trial was stopped early based on a recommendation by the Independent Data Monitoring Committee after the combination produced a significant OS improvement.

The primary analysis conducted at a median follow-up of 16 months, also showed an improvement in median progression-free survival with the combination, at 9 months vs 6 months with chemotherapy (HR, 0.48; 95% CI, 0.36-0.63). Similarly, the objective response rate was improved with the addition of cemiplimab, at 48% vs 23% with chemotherapy. The median duration of response was 16 months (range, 2-19+) with cemiplimab vs 5 months with chemotherapy (range, 2-19+).

With an additional 12 months of follow-up, findings from the prespecified final analysis continued to show that patients with PD-L1–positive disease derived clinically meaningful OS and PFS benefits with the cemiplimab regimen compared with chemotherapy alone.

Regarding safety, immune-mediated adverse effects (AEs) occurring in at least 10% of patients included anemia (44%), alopecia (37%), musculoskeletal pain (27%), nausea (25%), fatigue (23%), peripheral neuropathy (21%), hyperglycemia (18%), decreased appetite (17%), alanine aminotransferase increase (16%), aspartate aminotransferase increase (15%), neutropenia (15%), constipation (14%), dyspnea (13%), rash (13%), thrombocytopenia (13%), vomiting (12%), diarrhea (11%), insomnia (11%), weight decreased (11%), and hypoalbuminemia (10%). Serious AEs occurred in 25% of patients and led to permanent discontinuation of the investigational regimen in 5% of patients.

“The phase 3 EMPOWER-Lung 3 trial showed significant improvements across primary and key secondary end points, including overall survival in the cemiplimab plus chemotherapy arm,” Martin Reck, MD, PhD, head, Department of Thoracic Oncology, Lung Clinic Grosshansdorf in Germany, stated. “As a treating physician of this patient population, I welcome a new treatment option for patients in Europe, as we continue to strive for better outcomes for patients with advanced non-small cell lung cancer.”

In December 2022, cemiplimab plus chemotherapy was added to the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (score: 4 out of 5), for patients with advanced NSCLC across squamous and nonsquamous histologies, and irrespective of PD-L1 expression levels.

“With lung cancer being the leading cause of cancer mortality globally, ongoing research is imperative to find more treatment options for people impacted by this disease,” Anne-Marie Baird, PhD, president, Lung Cancer Europe, added. “This approval highlights continued progress in first-line treatment options for people impacted by advanced lung cancer in Europe.”

Early in March 2023, , the FDA approved the VENTANA PD-L1 (SP263) assay to help identify patients with advanced NSCLC who may be candidates for treatment with cemiplimab.²

References

1. Libtayo® (cemiplimab) in combination with chemotherapy approved by European Commission for the first-line treatment of advanced PD-L1 positive non-small cell lung cancer (NSCLC). News release. Regeneron Pharmaceuticals. March 29, 2023. Accessed March 29, 2023. https://www.globenewswire.com/news-release
2. Roche receives FDA approval of label expansion for VENTANA PD- L1 (SP263) assay to identify patients with locally advanced and metastatic non-small cell lung cancer eligible for Libtayo. News release. Roche. March 6, 2023. Accessed March 29, 2023. https://diagnostics.roche.com/global/en/news-listing/