Avelumab versus docetaxel in patients with platinum-treated advanced non-small-cell lung cancer (JAVELIN Lung 200): an open-label, randomised, phase 3 study

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dc.contributor.authorBarlesi, Fabrice
dc.contributor.authorVansteenkiste, Johan
dc.contributor.authorSpigel, David
dc.contributor.authorIshii, Hidenobu
dc.contributor.authorGarassino, Marina
dc.contributor.authorde Marinis, Filippo
dc.contributor.authorOzguroglu, Mustafa
dc.contributor.authorSzczesna, Aleksandra
dc.contributor.authorPolychronis, Andreas
dc.contributor.authorUslu, Ruchan
dc.contributor.authorKrzakowski, Maciej
dc.contributor.authorLee, Jong-Seok
dc.contributor.authorCalabro, Luana
dc.contributor.authorFrontera, Osvaldo Aren
dc.contributor.authorEllers-Lenz, Barbara
dc.contributor.authorBajars, Marcis
dc.contributor.authorRuisi, Mary
dc.contributor.authorPark, Keunchil
dc.date.accessioned2019-10-27T10:01:01Z
dc.date.available2019-10-27T10:01:01Z
dc.date.issued2018
dc.departmentEge Üniversitesien_US
dc.description.abstractBackground Antibodies targeting the immune checkpoint molecules PD-1 or PD-L1 have demonstrated clinical efficacy in patients with metastatic non-small-cell lung cancer (NSCLC). In this trial we investigated the efficacy and safety of avelumab, an anti-PD-L1 antibody, in patients with NSCLC who had already received platinum-based therapy. Methods JAVELIN Lung 200 was a multicentre, open-label, randomised, phase 3 trial at 173 hospitals and cancer treatment centres in 31 countries. Eligible patients were aged 18 years or older and had stage IIIB or IV or recurrent NSCLC and disease progression after treatment with a platinum-containing doublet, an Eastern Cooperative Oncology Group performance status score of 0 or 1, an estimated life expectancy of more than 12 weeks, and adequate haematological, renal, and hepatic function. Participants were randomly assigned (1:1), via an interactive voice-response system with a stratified permuted block method with variable block length, to receive either avelumab 10 mg/kg every 2 weeks or docetaxel 75 mg/m(2) every 3 weeks. Randomisation was stratified by PD-L1 expression (>= 1% vs < 1% of tumour cells), which was measured with the 73-10 assay, and histology (squamous vs non-squamous). The primary endpoint was overall survival, analysed when roughly 337 events (deaths) had occurred in the PD-L1-positive population. Efficacy was analysed in all PD-L1-positive patients (ie, PD-L1 expression in >= 1% of tumour cells) randomly assigned to study treatment (the primary analysis population) and then in all randomly assigned patients through a hierarchical testing procedure. Safety was analysed in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT02395172. Enrolment is complete, but the trial is ongoing. Findings Between March 24, 2015, and Jan 23, 2017, 792 patients were enrolled and randomly assigned to receive avelumab (n=396) or docetaxel (n=396). 264 participants in the avelumab group and 265 in the docetaxel group had PD-L1-positive tumours. In patients with PD-L1-positive tumours, median overall survival did not differ significantly between the avelumab and docetaxel groups (11.4 months [95% CI 9.4-13.9] vs 10.3 months [8.5-13.0]; hazard ratio 0.90 [96% CI 0.72-1.12]; one-sided p=0.16). Treatment-related adverse events occurred in 251 (64%) of 393 avelumab-treated patients and 313 (86%) of 365 docetaxel-treated patients, including grade 3-5 events in 39 (10%) and 180 (49%) patients, respectively. The most common grade 3-5 treatment-related adverse events were infusion-related reaction (six patients [2%]) and increased lipase (four [1%]) in the avelumab group and neutropenia (51 [14%]), febrile neutropenia (37 [10%]), and decreased neutrophil counts (36 [10%]) in the docetaxel group. Serious treatment-related adverse events occurred in 34 (9%) patients in the avelumab group and 75 (21%) in the docetaxel group. Treatment-related deaths occurred in four (1%) participants in the avelumab group, two due to interstitial lung disease, one due to acute kidney injury, and one due to a combination of autoimmune myocarditis, acute cardiac failure, and respiratory failure. Treatment-related deaths occurred in 14 (4%) patients in the docetaxel group, three due to pneumonia, and one each due to febrile neutropenia, septic shock, febrile neutropenia with septic shock, acute respiratory failure, cardiovascular insufficiency, renal impairment, leucopenia with mucosal inflammation and pyrexia, infection, neutropenic infection, dehydration, and unknown causes. Interpretation Compared with docetaxel, avelumab did not improve overall survival in patients with platinum-treated PD-L1-positive NSCLC, but had a favourable safety profile. Copyright (C) 2018 Elsevier Ltd. All rights reserved.en_US
dc.description.sponsorshipMerckMerck & Company; PfizerPfizeren_US
dc.description.sponsorshipMerck and Pfizer.en_US
dc.identifier.doi10.1016/S1470-2045(18)30673-9en_US
dc.identifier.endpage1479en_US
dc.identifier.issn1470-2045
dc.identifier.issn1474-5488
dc.identifier.issue11en_US
dc.identifier.pmid30262187en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage1468en_US
dc.identifier.urihttps://doi.org/10.1016/S1470-2045(18)30673-9
dc.identifier.urihttps://hdl.handle.net/11454/29796
dc.identifier.volume19en_US
dc.identifier.wosWOS:000449100300044en_US
dc.identifier.wosqualityQ1en_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.titleAvelumab versus docetaxel in patients with platinum-treated advanced non-small-cell lung cancer (JAVELIN Lung 200): an open-label, randomised, phase 3 studyen_US
dc.typeArticleen_US

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