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dc.contributor.authorHussain, SA
dc.contributor.authorLester, JF
dc.contributor.authorJackson, R
dc.contributor.authorGornall, M
dc.contributor.authorQureshi, M
dc.contributor.authorElliott, A
dc.contributor.authorCrabb, SJ
dc.contributor.authorHuddart, RA
dc.contributor.authorVasudev, N
dc.contributor.authorBirtle, AJ
dc.contributor.authorWorlding, J
dc.contributor.authorJames, ND
dc.contributor.authorParikh, O
dc.contributor.authorVilarino-Varela, M
dc.contributor.authorAlonzi, R
dc.contributor.authorLinch, MD
dc.contributor.authorRiaz, IB
dc.contributor.authorCatto, JWF
dc.contributor.authorPowles, T
dc.contributor.authorJones, RJ
dc.coverage.spatialEngland
dc.date.accessioned2022-07-13T14:01:43Z
dc.date.available2022-07-13T14:01:43Z
dc.date.issued2022-05-01
dc.identifierS1470-2045(22)00158-9
dc.identifier.citationThe Lancet Oncology, 2022, 23 (5), pp. 650 - 658en_US
dc.identifier.issn1470-2045
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/5223
dc.identifier.eissn1474-5488
dc.identifier.eissn1474-5488
dc.identifier.doi10.1016/S1470-2045(22)00158-9
dc.identifier.doi10.1016/S1470-2045(22)00158-9
dc.description.abstractBACKGROUND: Recurrence is common after neoadjuvant chemotherapy and radical treatment for muscle-invasive bladder cancer. We investigated the effect of adding nintedanib to neoadjuvant chemotherapy on response and survival in muscle-invasive bladder cancer. METHODS: NEOBLADE was a parallel-arm, double-blind, randomised, placebo-controlled, phase 2 trial of neoadjuvant gemcitabine and cisplatin chemotherapy with nintedanib or placebo in locally advanced muscle-invasive bladder cancer. Patients aged 18 years or older, with an Eastern Cooperative Oncology Group performance status of 0-1, were recruited from 15 hospitals in the UK. Patients were randomly assigned (1:1) to nintedanib or placebo using permuted blocks with random block sizes of two or four, stratified by centre and glomerular filtration rate. Treatments were allocated using an interactive web-based system, and patients and investigators were masked to treatment allocation throughout the study. Patients received oral nintedanib (150 mg or 200 mg twice daily for 12 weeks) or placebo, in addition to usual neoadjuvant chemotherapy with intravenous gemcitabine 1000 mg/m2 on days 1 and 8 and intravenous cisplatin 70 mg/m2 on day 1 of a 3-weekly cycle. The primary endpoint was pathological complete response rate, assessed at cystectomy or at day 8 of cyclde 3 (plus or minus 7 days) if cystectomy did not occur. Primary analyses were done in the intention-to-treat population. The trial is registered with EudraCT, 2012-004895-01, and ISRCTN, 56349930, and has completed planned recruitment. FINDINGS: Between Dec 4, 2014, and Sept 3, 2018, 120 patients were recruited and were randomly allocated to receive nintedanib (n=57) or placebo (n=63). The median follow-up for the study was 33·5 months (IQR 14·0-44·0). Pathological complete response in the intention-to-treat population was reached in 21 (37%) of 57 patients in the nintedanib group and 20 (32%) of 63 in the placebo group (odds ratio [OR] 1·25, 70% CI 0·84-1·87; p=0·28). Grade 3 or worse toxicities were observed in 53 (93%) of 57 participants who received nintedanib and 50 (79%) of 63 patients in the placebo group (OR 1·65, 95% CI 0·74-3·65; p=0·24). The most common grade 3 or worse adverse events were thromboembolic events (17 [30%] of 57 patients in the nintedanib group vs 13 [21%] of 63 patients in the placebo group [OR 1·63, 95% CI 0·71-3·76; p=0·29]) and decreased neutrophil count (22 [39%] in the nintedanib group vs seven [11%] in the placebo group [5·03, 1·95-13·00; p=0·0006]). 45 treatment-related serious adverse events occurred in the nintedanib group and 43 occurred in the placebo group. One treatment-related death occurred in the placebo group, which was due to myocardial infarction. INTERPRETATION: The addition of nintedanib to chemotherapy was safe but did not improve the rate of pathological complete response in muscle-invasive bladder cancer. FUNDING: Boehringer Ingelheim.
dc.formatPrint-Electronic
dc.format.extent650 - 658
dc.languageeng
dc.language.isoengen_US
dc.publisherElsevier BVen_US
dc.relation.ispartofThe Lancet Oncology
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectCisplatin
dc.subjectDeoxycytidine
dc.subjectDouble-Blind Method
dc.subjectFemale
dc.subjectHumans
dc.subjectIndoles
dc.subjectMale
dc.subjectMuscles
dc.subjectNeoadjuvant Therapy
dc.subjectUrinary Bladder Neoplasms
dc.titleAddition of nintedanib or placebo to neoadjuvant gemcitabine and cisplatin in locally advanced muscle-invasive bladder cancer (NEOBLADE): a double-blind, randomised, phase 2 trial.en_US
dc.typeJournal Article
dcterms.dateAccepted2022-03-10
dc.date.updated2022-07-13T13:53:06Z
rioxxterms.versionVoRen_US
rioxxterms.versionofrecord10.1016/S1470-2045(22)00158-9en_US
rioxxterms.licenseref.startdate2022-05-01
rioxxterms.typeJournal Article/Reviewen_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/35421369
pubs.issue5
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Clinical Academic Radiotherapy (Huddart)
pubs.publication-statusPublished
pubs.volume23
icr.researchteamClinic Acad RT Huddarten_US
dc.contributor.icrauthorHuddart, Robert
icr.provenanceDeposited by Mr Arek Surman on 2022-07-13. Deposit type is initial. No. of files: 1. Files: 1-s2.0-S1470204522001589-main.pdf


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