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

Autor:	Barlesi F; Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France., Vansteenkiste J; Department of Respiratory Oncology, University Hospital KU Leuven, Leuven, Belgium., Spigel D; Sarah Cannon Research Institute, Nashville, TN, USA., Ishii H; Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan., Garassino M; Thoracic Oncology Unit, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., de Marinis F; Thoracic Oncology Division, European Institute of Oncology, Milan, Italy., Özgüroğlu M; Department of Internal Medicine, Division of Medical Oncology, Cerrahpaşa Medical Faculty, Istanbul University, Istanbul, Turkey., Szczesna A; Department of Lung Diseases, Regional Lung Disease Hospital, Otwock, Poland., Polychronis A; Department of Medical Oncology, Mount Vernon Cancer Centre, Northwood, Middlesex, UK., Uslu R; Ege University Hospital, Department of Medical Oncology, Izmir, Turkey., Krzakowski M; Centrum Onkologii-Instytut Im M Skłodowskiej-Curie w Warszawie, Warsaw, Poland., Lee JS; Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, South Korea., Calabrò L; Center for Immuno-Oncology, Medical Oncology and Immunotherapy, University Hospital of Siena, Siena, Italy., Arén Frontera O; Centro Investigación Clínica Bradford Hill, Santiago, Chile., Ellers-Lenz B; Merck, Darmstadt, Germany., Bajars M; EMD Serono, Billerica, MA, USA., Ruisi M; EMD Serono, Billerica, MA, USA., Park K; Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Electronic address: kpark@skku.edu.
Jazyk:	angličtina
Zdroj:	The Lancet. Oncology [Lancet Oncol] 2018 Nov; Vol. 19 (11), pp. 1468-1479. Date of Electronic Publication: 2018 Sep 24.
DOI:	10.1016/S1470-2045(18)30673-9
Abstrakt:	Background: 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. Funding: Merck and Pfizer. (Copyright © 2018 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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