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Tipifarnib in Head and Neck Squamous Cell Carcinoma With HRAS Mutations

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Abstract
PURPOSE Mutations in the HRAS (mHRAS) proto-oncogene occur in 4%-8% of patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Tipifarnib is a farnesyltransferase inhibitor that disrupts HRAS function. We evaluated the efficacy of tipifarnib in patients with R/M mHRAS HNSCC.

METHODS We enrolled 30 patients with R/M HNSCC in a single-arm, open-label phase II trial of tipifarnib for mHRAS malignancies; one additional patient was treated on an expanded access program. After an ad hoc analysis of the first 16 patients with HNSCC with mHRAS variant allele frequency (VAF) data, enrollment was limited to those with a mHRAS VAF of >= 20% (high VAF). The primary end point was objective response rate. Secondary end points included assessing safety and tolerability. Patients received tipifarnib 600 or 900 mg orally twice daily on days 1-7 and 15-21 of 28-day cycles.

RESULTS Of the 22 patients with HNSCC with high VAF, 20 were evaluable for response at the time of data cutoff. Objective response rate for evaluable patients with high-VAF HNSCC was 55% (95% CI, 31.5 to 76.9). Median progression-free survival on tipifarnib was 5.6 months (95% CI, 3.6 to 16.4) versus 3.6 months (95% CI, 1.3 to 5.2) on last prior therapy. Median overall survival was 15.4 months (95% CI, 7.0 to 29.7). The most frequent treatment-emergent adverse events among the 30 patients with HNSCC were anemia (37%) and lymphopenia (13%).

CONCLUSION Tipifarnib demonstrated encouraging efficacy in patients with R/M HNSCC with HRAS mutations for whom limited therapeutic options exist. (C) 2021 by American Society of Clinical Oncology
Author(s)
김성배Alan L HoAntonio GualbertoBinaifer BalsaraBridget MartellCaroline EvenCatherine ScholzDeborah J WongFrancis WordenIoanna NixonIrene BranaJerome FayetteJessica BaumanKeith BibleKevin HarringtonLisa LicitraMaria Jose FlorMollie LeoniMyung-Ju AhnNabil F SabaPol SpecenierRober
Issued Date
2021
Type
Article
Keyword
울산의대 미표기 반려
URI
https://oak.ulsan.ac.kr/handle/2021.oak/8428
Publisher
JOURNAL OF CLINICAL ONCOLOGY
Location
미국
Language
영어
ISSN
0732-183X
Citation Volume
39
Citation Number
17
Citation Start Page
1856
Citation End Page
1856
Appears in Collections:
Medicine > Medicine
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