Ahmet Sezer1, Saadettin Kilickap2, Mahmut Gümüş3, Igor Bondarenko4, Mustafa Özgüroğlu5, Miranda Gogishvili6, Haci M Turk7, Irfan Cicin8, Dmitry Bentsion9, Oleg Gladkov10, Philip Clingan11, Virote Sriuranpong12, Naiyer Rizvi13, Bo Gao14, Siyu Li14, Sue Lee14, Kristina McGuire15, Chieh-I Chen14, Tamta Makharadze16, Semra Paydas17, Marina Nechaeva18, Frank Seebach15, David M Weinreich15, George D Yancopoulos15, Giuseppe Gullo15, Israel Lowy15, Petra Rietschel15. 1. Department of Medical Oncology, Başkent University, Adana, Turkey. Electronic address: drasezer@hotmail.com.tr. 2. Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkey. 3. Department of Medical Oncology, School of Medicine, Istanbul Medeniyet University, Istanbul, Turkey. 4. Department of Oncology and Medical Radiology; Dnipropetrovsk Medical Academy, Dnipro, Ukraine. 5. Cerrahpaşa Medical Faculty, Istanbul University-Cerrahpaşa, Istanbul, Turkey. 6. High Technology Medical Centre, University Clinic, Tbilisi, Georgia. 7. Department of Medical Oncology, Bezmialem Vakif University, Medical Faculty, Istanbul, Turkey. 8. Department of Medical Oncology, Trakya University, Edirne, Turkey. 9. Radiotherapy Department, Sverdlovsk Regional Oncology Centre, Sverdlovsk, Russia. 10. LLC, "EVIMED", Chelyabinsk, Russia. 11. Southern Medical Day Care Centre and Illawarra Health and Medical Research Institute, University of Wollongong-Illawarra Cancer Centre, Wollongong Hospital, Wollongong, NSW, Australia. 12. Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and the King Chulalongkorn Memorial Hospital, Bangkok, Thailand. 13. Division of Hematology-Oncology, Columbia University Medical Center, New York, New York, NY, USA. 14. Regeneron Pharmaceuticals, Basking Ridge, New Jersey, USA. 15. Regeneron Pharmaceuticals, Tarrytown, New York, NY, USA. 16. High Technology Hospital Medcenter, Batumi, Georgia. 17. Department of Medical Oncology, Faculty of Medicine, Cukurova University, Adana, Turkey. 18. Arkhangelsk Clinical Oncology Center, Arkhangelsk, Russia.
Abstract
BACKGROUND: We aimed to examine cemiplimab, a programmed cell death 1 inhibitor, in the first-line treatment of advanced non-small-cell lung cancer with programmed cell death ligand 1 (PD-L1) of at least 50%. METHODS: In EMPOWER-Lung 1, a multicentre, open-label, global, phase 3 study, eligible patients recruited in 138 clinics from 24 countries (aged ≥18 years with histologically or cytologically confirmed advanced non-small-cell lung cancer, an Eastern Cooperative Oncology Group performance status of 0-1; never-smokers were ineligible) were randomly assigned (1:1) to cemiplimab 350 mg every 3 weeks or platinum-doublet chemotherapy. Crossover from chemotherapy to cemiplimab was allowed following disease progression. Primary endpoints were overall survival and progression-free survival per masked independent review committee. Primary endpoints were assessed in the intention-to-treat population and in a prespecified PD-L1 of at least 50% population (per US Food and Drug Administration request to the sponsor), which consisted of patients with PD-L1 of at least 50% per 22C3 assay done according to instructions for use. Adverse events were assessed in all patients who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, NCT03088540 and is ongoing. FINDINGS:Between June 27, 2017 and Feb 27, 2020, 710 patients were randomly assigned (intention-to-treat population). In the PD-L1 of at least 50% population, which consisted of 563 patients, median overall survival was not reached (95% CI 17·9-not evaluable) with cemiplimab (n=283) versus 14·2 months (11·2-17·5) with chemotherapy (n=280; hazard ratio [HR] 0·57 [0·42-0·77]; p=0·0002). Median progression-free survival was 8·2 months (6·1-8·8) with cemiplimab versus 5·7 months (4·5-6·2) with chemotherapy (HR 0·54 [0·43-0·68]; p<0·0001). Significant improvements in overall survival and progression-free survival were also observed with cemiplimab in the intention-to-treat population despite a high crossover rate (74%). Grade 3-4 treatment-emergent adverse events occurred in 98 (28%) of 355 patients treated with cemiplimab and 135 (39%) of 342 patients treated with chemotherapy. INTERPRETATION:Cemiplimab monotherapy significantly improved overall survival and progression-free survival compared with chemotherapy in patients with advanced non-small-cell lung cancer with PD-L1 of at least 50%, providing a potential new treatment option for this patient population. FUNDING: Regeneron Pharmaceuticals and Sanofi.
RCT Entities:
BACKGROUND: We aimed to examine cemiplimab, a programmed cell death 1 inhibitor, in the first-line treatment of advanced non-small-cell lung cancer with programmed cell death ligand 1 (PD-L1) of at least 50%. METHODS: In EMPOWER-Lung 1, a multicentre, open-label, global, phase 3 study, eligible patients recruited in 138 clinics from 24 countries (aged ≥18 years with histologically or cytologically confirmed advanced non-small-cell lung cancer, an Eastern Cooperative Oncology Group performance status of 0-1; never-smokers were ineligible) were randomly assigned (1:1) to cemiplimab 350 mg every 3 weeks or platinum-doublet chemotherapy. Crossover from chemotherapy to cemiplimab was allowed following disease progression. Primary endpoints were overall survival and progression-free survival per masked independent review committee. Primary endpoints were assessed in the intention-to-treat population and in a prespecified PD-L1 of at least 50% population (per US Food and Drug Administration request to the sponsor), which consisted of patients with PD-L1 of at least 50% per 22C3 assay done according to instructions for use. Adverse events were assessed in all patients who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, NCT03088540 and is ongoing. FINDINGS: Between June 27, 2017 and Feb 27, 2020, 710 patients were randomly assigned (intention-to-treat population). In the PD-L1 of at least 50% population, which consisted of 563 patients, median overall survival was not reached (95% CI 17·9-not evaluable) with cemiplimab (n=283) versus 14·2 months (11·2-17·5) with chemotherapy (n=280; hazard ratio [HR] 0·57 [0·42-0·77]; p=0·0002). Median progression-free survival was 8·2 months (6·1-8·8) with cemiplimab versus 5·7 months (4·5-6·2) with chemotherapy (HR 0·54 [0·43-0·68]; p<0·0001). Significant improvements in overall survival and progression-free survival were also observed with cemiplimab in the intention-to-treat population despite a high crossover rate (74%). Grade 3-4 treatment-emergent adverse events occurred in 98 (28%) of 355 patients treated with cemiplimab and 135 (39%) of 342 patients treated with chemotherapy. INTERPRETATION:Cemiplimab monotherapy significantly improved overall survival and progression-free survival compared with chemotherapy in patients with advanced non-small-cell lung cancer with PD-L1 of at least 50%, providing a potential new treatment option for this patient population. FUNDING: Regeneron Pharmaceuticals and Sanofi.
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