Publications

Detailed Information

Safety and efficacy of nazartinib (EGF816) in adults with EGFR-mutant non-small-cell lung carcinoma: a multicentre, open-label, phase 1 study

DC Field Value Language
dc.contributor.authorTan, Daniel S-W-
dc.contributor.authorLeighl, Natasha B.-
dc.contributor.authorRiely, Gregory J.-
dc.contributor.authorYang, James C-H-
dc.contributor.authorSequist, Lecia, V-
dc.contributor.authorWolf, Juergen-
dc.contributor.authorSeto, Takashi-
dc.contributor.authorFelip, Enriqueta-
dc.contributor.authorAix, Santiago P.-
dc.contributor.authorJonnaert, Maud-
dc.contributor.authorPan, Chun-
dc.contributor.authorTan, Eugene Y.-
dc.contributor.authorKo, Jinnie-
dc.contributor.authorMoody, Susan E.-
dc.contributor.authorKim, Dong-Wan-
dc.date.accessioned2021-01-31T08:06:56Z-
dc.date.available2021-01-31T08:06:56Z-
dc.date.created2020-07-06-
dc.date.created2020-07-06-
dc.date.issued2020-06-
dc.identifier.citationThe Lancet Respiratory Medicine, Vol.8 No.6, pp.561-572-
dc.identifier.issn2213-2600-
dc.identifier.other105119-
dc.identifier.urihttps://hdl.handle.net/10371/171817-
dc.description.abstractBackground Resistance to first-generation and second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is mediated by the emergence of the Thr790Met mutation in 50-60% of treated patients with non-small-cell lung cancer (NSCLC). We aimed to assess the safety and activity of nazartinib (EGF816), a third-generation EGFR TKI that selectively inhibits EGFR with Thr790Met or activating mutations (or both), while sparing wild-type EGFR, in patients with advanced EGFR-mutant NSCLC. Methods This phase 1 dose-escalation part of an open-label, multicentre, phase 1/2 study was conducted at nine academic medical centres located in Europe, Asia, and North America. Patients were included if they were aged 18 years or older and had stage IIIB-IV EGFR-mutant NSCLC (with varying statuses of EGFR mutation and previous therapy allowed), at least one measurable lesion, and an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less. Nazartinib (at seven dose levels between 75 mg and 350 mg, in capsule or tablet form) was administered orally, once daily, on a continuous 28-day dosing schedule. A two-parameter Bayesian logistic regression model, guided by the escalation with overdose control principle, was implemented to make dose recommendations and estimate the maximum tolerated dose or recommended phase 2 dose of nazartinib (the primary outcome). This study is registered with ClinicalTrials.gov (NCT02108964); enrolment to phase 1 is complete and the study is ongoing. Findings By Aug 31, 2017, 180 patients (116 [64%] women; median age 60 years (52-69); 116 [64%] with ECOG performance status 1) received nazartinib across seven dose levels: 75 mg (n=17), 100 mg (n=38), 150 mg (n=73), 200 mg (n=8), 225 mg (n=28), 300 mg (n=5), and 350 mg (n=11). Seven dose-limiting toxicities were observed in six (3%) patients who received 150 mg, 225 mg, or 350 mg nazartinib once daily. Although the maximum tolerated dose was not met, the recommended phase 2 dose was declared as 150 mg once daily (tablet). The most common adverse events, regardless of cause, were rash (all subcategories 111 [62%] patients, maculopapular rash 72 [40%], dermatitis acneiform 22 [12%]), diarrhoea (81 [45%]), pruritus (70 [39%]), fatigue (54 [30%]), and stomatitis (54 [30%]), and were mostly grades 1-2. Any-cause grade 3-4 adverse events were reported in 99 (55%) patients across all doses, the most common being rash (all subcategories grouped 27 [15%]), pneumonia (12 [7%]), anaemia (ten [6%]), and dyspnoea (nine [5%]). Serious adverse events suspected to be drug-related occurred in 16 (9%) patients. Interpretation Nazartinib has a favourable safety profile, with low-grade skin toxicity characterised by a predominantly maculopapular rash that required minimal dose reductions. Copyright (C) 2020 Elsevier Ltd. All rights reserved.-
dc.language영어-
dc.publisherElsevier Limited-
dc.titleSafety and efficacy of nazartinib (EGF816) in adults with EGFR-mutant non-small-cell lung carcinoma: a multicentre, open-label, phase 1 study-
dc.typeArticle-
dc.contributor.AlternativeAuthor김동완-
dc.identifier.doi10.1016/S2213-2600(19)30267-X-
dc.citation.journaltitleThe Lancet Respiratory Medicine-
dc.identifier.wosid000540618400029-
dc.identifier.scopusid2-s2.0-85085950394-
dc.citation.endpage572-
dc.citation.number6-
dc.citation.startpage561-
dc.citation.volume8-
dc.identifier.sci000540618400029-
dc.description.isOpenAccessY-
dc.contributor.affiliatedAuthorKim, Dong-Wan-
dc.type.docTypeArticle-
dc.description.journalClass1-
dc.subject.keywordPlusCANCER-
dc.subject.keywordPlusRESISTANCE-
dc.subject.keywordPlusMUTATIONS-
dc.subject.keywordPlusOSIMERTINIB-
dc.subject.keywordPlusROCILETINIB-
dc.subject.keywordPlusINHIBITORS-
dc.subject.keywordPlusAZD9291-
Appears in Collections:
Files in This Item:
There are no files associated with this item.

Altmetrics

Item View & Download Count

  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Share