Cited 23 times in
A phase Ib study of the combination of afatinib and ruxolitinib in EGFR mutant NSCLC with progression on EGFR-TKIs
DC Field | Value | Language |
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dc.contributor.author | 김혜련 | - |
dc.contributor.author | 조병철 | - |
dc.contributor.author | 홍민희 | - |
dc.date.accessioned | 2019-09-20T07:41:43Z | - |
dc.date.available | 2019-09-20T07:41:43Z | - |
dc.date.issued | 2019 | - |
dc.identifier.issn | 0169-5002 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/171017 | - |
dc.description.abstract | OBJECTIVES: We evaluated the safety and efficacy of the combination therapy of afatinib, an irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), and ruxolitinib, a JAK1/2 selective inhibitor, in patients with EGFR mutant NSCLC progressing on at least one kind of EGFR-TKI. MATERIALS AND METHODS: In this phase Ib open-label study, we used a 3 + 3 dose-escalation design. Patients with histologically diagnosed EGFR-mutant stage IV NSCLC and documented disease progression on EGFR-TKI therapies were enrolled. Afatinib only was administered on day 1 through day 8 (run-in period), then ruxolitinib was administered concurrently with afatinib until disease progression. The primary endpoints were to determine the dose-limiting toxicity (DLT) and a recommended phase II dose of the combination regimen. We also included a dose confirmation cohort for the highest dose, and an expansion cohort for T790 M mutation. RESULTS: As of October 2017, 30 patients participated in the study, of which 20 had T790 M mutations. Because no DLT was observed in nine patients at the highest dose level (50 mg afatinib once daily plus 25 mg ruxolitinib twice daily), nine patients with T790 M mutations were enrolled in a dose-expansion cohort. Frequent adverse events included diarrhea (G3 in 3 of 22 cases), anemia (G3 in 1 of 26 cases), paronychia (G1/2 in 14 cases), acneiform rash (G1 in 13 cases), and oral mucositis (G1/2 in 12 cases). Objective response rate was 23.3% (no complete response [CR] and 7 partial responses [PR]) and disease control rate was 93.3% (no CR, 7 PR and 21 stable diseases). The median progression-free survival was 4.9 months (95% CI, 2.4-7.5). CONCLUSION: The combination of afatinib and ruxolitinib was tolerated by patients, with modest clinical activity observed in NSCLC with acquired resistance to EGFR-TKIs (NCT02145637). | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | Elsevier Scientific Publishers | - |
dc.relation.isPartOf | Lung Cancer | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.title | A phase Ib study of the combination of afatinib and ruxolitinib in EGFR mutant NSCLC with progression on EGFR-TKIs | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | Ji Soo Park | - |
dc.contributor.googleauthor | Min Hee Hong | - |
dc.contributor.googleauthor | You Jin Chun | - |
dc.contributor.googleauthor | Hye Ryun Kim | - |
dc.contributor.googleauthor | Byoung Chul Cho | - |
dc.identifier.doi | 10.1016/j.lungcan.2019.05.030 | - |
dc.contributor.localId | A01166 | - |
dc.contributor.localId | A03822 | - |
dc.contributor.localId | A04393 | - |
dc.relation.journalcode | J02174 | - |
dc.identifier.eissn | 1872-8332 | - |
dc.identifier.pmid | 31319994 | - |
dc.identifier.url | https://www.sciencedirect.com/science/article/pii/S016950021930474X | - |
dc.subject.keyword | Afatinib | - |
dc.subject.keyword | EGFR | - |
dc.subject.keyword | Non-Small cell lung cancer (NSCLC) | - |
dc.subject.keyword | Ruxolitinib | - |
dc.subject.keyword | T790M | - |
dc.contributor.alternativeName | Kim, Hye Ryun | - |
dc.contributor.affiliatedAuthor | 김혜련 | - |
dc.contributor.affiliatedAuthor | 조병철 | - |
dc.contributor.affiliatedAuthor | 홍민희 | - |
dc.citation.volume | 134 | - |
dc.citation.startPage | 46 | - |
dc.citation.endPage | 51 | - |
dc.identifier.bibliographicCitation | Lung Cancer, Vol.134 : 46-51, 2019 | - |
dc.identifier.rimsid | 63976 | - |
dc.type.rims | ART | - |
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