A Phase II Trial of Tipifarnib for Patients with Previously Treated, Metastatic Urothelial Carcinoma Harboring HRAS Mutations
DC Field | Value | Language |
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dc.contributor.author | Lee, Hye Won | - |
dc.contributor.author | Sa, Jason K. | - |
dc.contributor.author | Gualberto, Antonio | - |
dc.contributor.author | Scholz, Catherine | - |
dc.contributor.author | Sung, Hyun Hwan | - |
dc.contributor.author | Jeong, Byong Chang | - |
dc.contributor.author | Choi, Han Yong | - |
dc.contributor.author | Kwon, Ghee Young | - |
dc.contributor.author | Park, Se Hoon | - |
dc.date.accessioned | 2021-08-30T12:13:15Z | - |
dc.date.available | 2021-08-30T12:13:15Z | - |
dc.date.created | 2021-06-19 | - |
dc.date.issued | 2020-10-01 | - |
dc.identifier.issn | 1078-0432 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/52498 | - |
dc.description.abstract | Purpose: To assess the antitumor activity and safety of tipifarnib, a highly potent and selective farnesyltransferase inhibitor, we performed a phase II clinical trial in patients with advanced and refractory urothelial carcinoma harboring missense HRAS mutations. Patients and Methods: A total of 245 adult patients with previously treated, advanced urothelial carcinoma entered the molecular screening program including HRAS. Those with missense HRAS mutations or STK11:rs2075606 received oral tipifarnib 900 mg twice daily on days 1-7 and 15-21 of 28-day treatment cycles. The primary endpoint was progression-free survival at 6 months (PFS6). Results: Weidentified 16 (7%) missense HRASmutations (G13R, 7; Q61R, 4; G12S, 3; G12C, 2) and 104 (46%) STK11:rs2075606 carriers. In 21 patients enrolled in the study, 14 and 7 patients had missense HRAS mutations and STK11:rs2075606, respectively. The most frequently observed adverse events included fatigue (86%) and hematologic toxicities. With a median follow-up of 28 months, 4 patients (19%) reached PFS6: 3 had missense HRAS mutations and one patient, enrolled as an STK11 carrier, had HRAS frameshift insertions at H27fs and H28fs rendering a nonsense HRAS mutation. The overall response rate by intent-totreat analysis was 24% (4 missense and one nonsense frameshift HRAS mutation); no response was observed in patients with urothelial carcinoma with wild- type HRAS tumors. Five responses were observed in 12 evaluable patients of 15 with tumors carrying HRAS mutations. Conclusions: Oral tipifarnib resulted in a manageable safety profile and encouraging antitumor efficacy against treatmentrefractory urothelial carcinoma containing HRAS mutations. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | AMER ASSOC CANCER RESEARCH | - |
dc.subject | FARNESYL TRANSFERASE INHIBITOR | - |
dc.subject | FARNESYLTRANSFERASE INHIBITORS | - |
dc.subject | MOLECULAR CHARACTERIZATION | - |
dc.subject | CANCER | - |
dc.subject | BLADDER | - |
dc.subject | R115777 | - |
dc.subject | GENES | - |
dc.subject | FGFR3 | - |
dc.subject | LKB1 | - |
dc.title | A Phase II Trial of Tipifarnib for Patients with Previously Treated, Metastatic Urothelial Carcinoma Harboring HRAS Mutations | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Sa, Jason K. | - |
dc.identifier.doi | 10.1158/1078-0432.CCR-20-1246 | - |
dc.identifier.scopusid | 2-s2.0-85101035551 | - |
dc.identifier.wosid | 000576795700010 | - |
dc.identifier.bibliographicCitation | CLINICAL CANCER RESEARCH, v.26, no.19, pp.5113 - 5119 | - |
dc.relation.isPartOf | CLINICAL CANCER RESEARCH | - |
dc.citation.title | CLINICAL CANCER RESEARCH | - |
dc.citation.volume | 26 | - |
dc.citation.number | 19 | - |
dc.citation.startPage | 5113 | - |
dc.citation.endPage | 5119 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.subject.keywordPlus | FARNESYL TRANSFERASE INHIBITOR | - |
dc.subject.keywordPlus | FARNESYLTRANSFERASE INHIBITORS | - |
dc.subject.keywordPlus | MOLECULAR CHARACTERIZATION | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | BLADDER | - |
dc.subject.keywordPlus | R115777 | - |
dc.subject.keywordPlus | GENES | - |
dc.subject.keywordPlus | FGFR3 | - |
dc.subject.keywordPlus | LKB1 | - |
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