A Phase II Trial of Tipifarnib for Patients with Previously Treated, Metastatic Urothelial Carcinoma Harboring HRAS Mutations
- Authors
- Lee, HW[Lee, Hye Won]; Sa, JK[Sa, Jason K.]; Gualberto, A[Gualberto, Antonio]; Scholz, C[Scholz, Catherine]; Sung, HH[Sung, Hyun Hwan]; Jeong, BC[Jeong, Byong Chang]; Choi, HY[Choi, Han Yong]; Kwon, GY[Kwon, Ghee Young]; Park, SH[Park, Se Hoon]
- Issue Date
- 1-Oct-2020
- Publisher
- AMER ASSOC CANCER RESEARCH
- Citation
- CLINICAL CANCER RESEARCH, v.26, no.19, pp.5113 - 5119
- Indexed
- SCIE
SCOPUS
- Journal Title
- CLINICAL CANCER RESEARCH
- Volume
- 26
- Number
- 19
- Start Page
- 5113
- End Page
- 5119
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/2078
- DOI
- 10.1158/1078-0432.CCR-20-1246
- ISSN
- 1078-0432
- 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.
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Collections - Medicine > Department of Medicine > 1. Journal Articles
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