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dc.contributor.authorHo, AL
dc.contributor.authorBrana, I
dc.contributor.authorHaddad, R
dc.contributor.authorBauman, J
dc.contributor.authorBible, K
dc.contributor.authorOosting, S
dc.contributor.authorWong, DJ
dc.contributor.authorAhn, M-J
dc.contributor.authorBoni, V
dc.contributor.authorEven, C
dc.contributor.authorFayette, J
dc.contributor.authorFlor, MJ
dc.contributor.authorHarrington, K
dc.contributor.authorKim, S-B
dc.contributor.authorLicitra, L
dc.contributor.authorNixon, I
dc.contributor.authorSaba, NF
dc.contributor.authorHackenberg, S
dc.contributor.authorSpecenier, P
dc.contributor.authorWorden, F
dc.contributor.authorBalsara, B
dc.contributor.authorLeoni, M
dc.contributor.authorMartell, B
dc.contributor.authorScholz, C
dc.contributor.authorGualberto, A
dc.date.accessioned2021-04-13T10:17:26Z
dc.date.available2021-04-13T10:17:26Z
dc.date.issued2021-03-22
dc.identifier.citationJournal of clinical oncology : official journal of the American Society of Clinical Oncology, 2021, pp. JCO2002903 - ?
dc.identifier.issn0732-183X
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4518
dc.identifier.eissn1527-7755
dc.identifier.eissn1527-7755en_US
dc.identifier.doi10.1200/jco.20.02903
dc.identifier.doi10.1200/jco.20.02903en_US
dc.description.abstractPurpose Mutations in the <i>HRAS</i> (m<i>HRAS</i>) 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 <i>HRAS</i> function. We evaluated the efficacy of tipifarnib in patients with R/M m<i>HRAS</i> HNSCC.Methods We enrolled 30 patients with R/M HNSCC in a single-arm, open-label phase II trial of tipifarnib for m<i>HRAS</i> malignancies; one additional patient was treated on an expanded access program. After an ad hoc analysis of the first 16 patients with HNSCC with m<i>HRAS</i> variant allele frequency (VAF) data, enrollment was limited to those with a m<i>HRAS</i> 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 <i>HRAS</i> mutations for whom limited therapeutic options exist (NCT02383927).
dc.formatPrint-Electronic
dc.format.extentJCO2002903 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleTipifarnib in Head and Neck Squamous Cell Carcinoma With <i>HRAS</i> Mutations.
dc.typeJournal Article
dcterms.dateAccepted2021-03-22
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1200/jco.20.02903
rioxxterms.licenseref.startdate2021-03-22
rioxxterms.licenseref.startdate2021-03-22en_US
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfJournal of clinical oncology : official journal of the American Society of Clinical Oncology
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Targeted Therapy
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Targeted Therapy
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Targeted Therapy
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Targeted Therapy
pubs.publication-statusPublished
pubs.embargo.termsNot known
icr.researchteamTargeted Therapy
icr.researchteamTargeted Therapyen_US
dc.contributor.icrauthorHarrington, Kevinen


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