First-line cemiplimab monotherapy and continued cemiplimab beyond progression plus chemotherapy for advanced non-small-cell lung cancer with PD-L1 50% or more (EMPOWER-Lung 1): 35-month follow-up from a multicentre, open-label, randomised, phase 3 trial

dc.authoridBondarenko, Igor/0000-0002-7071-2471
dc.authorwosidBondarenko, Igor/U-5156-2017
dc.contributor.authorOzguroglu, Mustafa
dc.contributor.authorKilickap, Saadettin
dc.contributor.authorSezer, Ahmet
dc.contributor.authorGumus, Mahmut
dc.contributor.authorBondarenko, Igor
dc.contributor.authorGogishvili, Miranda
dc.contributor.authorNechaeva, Marina
dc.date.accessioned2024-06-12T11:19:33Z
dc.date.available2024-06-12T11:19:33Z
dc.date.issued2023
dc.departmentTrakya Üniversitesien_US
dc.description.abstractBackground: Cemiplimab provided significant survival benefit to patients with advanced non-small-cell lung cancer with PD-L1 tumour expression of at least 50% and no actionable biomarkers at 1-year follow-up. In this exploratory analysis, we provide outcomes after 35 months' follow-up and the effect of adding chemotherapy to cemiplimab at the time of disease progression.Methods: EMPOWER-Lung 1 was a multicentre, open-label, randomised, phase 3 trial. We enrolled patients (aged >= 18 years) with histologically confirmed squamous or non-squamous advanced non-small-cell lung cancer with PD-L1 tumour expression of 50% or more. We randomly assigned (1:1) patients to intravenous cemiplimab 350 mg every 3 weeks for up to 108 weeks, or until disease progression, or investigator's choice of chemotherapy. Central randomisation scheme generated by an interactive web response system governed the randomisation process that was stratified by histology and geographical region. Primary endpoints were overall survival and progression free survival, as assessed by a blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumours version 1.1. Patients with disease progression on cemiplimab could continue cemiplimab with the addition of up to four cycles of chemotherapy. We assessed response in these patients by BICR against a new baseline, defined as the last scan before chemotherapy initiation. The primary endpoints were assessed in all randomly assigned participants (ie, intention-to-treat population) and in those with a PD-L1 expression of at least 50%. We assessed adverse events in all patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT03088540.Findings: Between May 29, 2017, and March 4, 2020, we recruited 712 patients (607 [85%] were male and 105 [15%] were female). We randomly assigned 357 (50%) to cemiplimab and 355 (50%) to chemotherapy. 284 (50%) patients assigned to cemiplimab and 281 (50%) assigned to chemotherapy had verified PD-L1 expression of at least 50%. At 35 months' follow-up, among those with a verified PD-L1 expression of at least 50% median overall survival in the cemiplimab group was 261 months (95% CI 221-318; 149 [52%] of 284 died) versus 133 months (105-162; 188 [67%] of 281 died) in the chemotherapy group (hazard ratio [HR] 057, 95% CI 046-071; p<00001), median progression-free survival was 81 months (95% CI 62-88; 214 events occurred) in the cemiplimab group versus 53 months (43-61; 236 events occurred) in the chemotherapy group (HR 051, 95% CI 042-062; p<00001). Continued cemiplimab plus chemotherapy as second-line therapy (n=64) resulted in a median progression-free survival of 66 months (61-93) and overall survival of 151 months (113-187). The most common grade 3-4 treatment-emergent adverse events were anaemia (15 [4%] of 356 patients in the cemiplimab group vs 60 [17%] of 343 in the control group), neutropenia (three [1%] vs 35 [10%]), and pneumonia (18 [5%] vs 13 [4%]). Treatment-related deaths occurred in ten (3%) of 356 patients treated with cemiplimab (due to autoimmune myocarditis, cardiac failure, cardio-respiratory arrest, cardiopulmonary failure, septic shock, tumour hyperprogression, nephritis, respiratory failure, [n=1 each] and general disorders or unknown [n=2]) and in seven (2%) of 343 patients treated with chemotherapy (due to pneumonia and pulmonary embolism [n=2 each], and cardiac arrest, lung abscess, and myocardial infarction [n=1 each]). The safety profile of cemiplimab at 35 months, and of continued cemiplimab plus chemotherapy, was generally consistent with that previously observed for these treatments, with no new safety signalsINTERPRETATION: At 35 months' follow-up, the survival benefit of cemiplimab for patients with advanced non-small-cell lung cancer was at least as pronounced as at 1 year, affirming its use as first-line monotherapy for this population. Adding chemotherapy to cemiplimab at progression might provide a new second-line treatment for patients with advanced non-small-cell lung cancer.Copyright (c) 2023 Elsevier Ltd. All rights reserved.en_US
dc.description.sponsorshipRegeneron Pharmaceuticals; Sanofien_US
dc.description.sponsorshipThe study was sponsored by Regeneron Pharmaceuticals and Sanofi and was designed by employees of Regeneron Pharmaceuticals in collaboration with the investigators. An independent masked independent review committee reviewed all tumour assessments to assess tumour response per RECIST version 1.1. Safety monitoring was done by an IDMC. The authors thank the patients, their families, all other investigators, and all investigational site members involved in this study. We acknowledge assistance with writing and developing the manuscript by Osnat Ben-Shahar, Regeneron Pharmaceuticals. Responsibility for all opinions, conclusions, and data interpretation lies with the authors.en_US
dc.identifier.doi10.1016/S1470-2045(23)00329-7
dc.identifier.endpage1001en_US
dc.identifier.issn1470-2045
dc.identifier.issn1474-5488
dc.identifier.issue9en_US
dc.identifier.pmid37591293en_US
dc.identifier.scopus2-s2.0-85170287771en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage989en_US
dc.identifier.urihttps://doi.org/10.1016/S1470-2045(23)00329-7
dc.identifier.urihttps://hdl.handle.net/20.500.14551/25253
dc.identifier.volume24en_US
dc.identifier.wosWOS:001120979900001en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherElsevier Science Incen_US
dc.relation.ispartofLancet Oncologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectPembrolizumaben_US
dc.subjectImmunotherapyen_US
dc.subjectOutcomesen_US
dc.subjectDeathen_US
dc.subjectAtezolizumaben_US
dc.subjectExpressionen_US
dc.titleFirst-line cemiplimab monotherapy and continued cemiplimab beyond progression plus chemotherapy for advanced non-small-cell lung cancer with PD-L1 50% or more (EMPOWER-Lung 1): 35-month follow-up from a multicentre, open-label, randomised, phase 3 trialen_US
dc.typeArticleen_US

Dosyalar