dc.contributor.author | Ho, AL | |
dc.contributor.author | Brana, I | |
dc.contributor.author | Haddad, R | |
dc.contributor.author | Bauman, J | |
dc.contributor.author | Bible, K | |
dc.contributor.author | Oosting, S | |
dc.contributor.author | Wong, DJ | |
dc.contributor.author | Ahn, M-J | |
dc.contributor.author | Boni, V | |
dc.contributor.author | Even, C | |
dc.contributor.author | Fayette, J | |
dc.contributor.author | Flor, MJ | |
dc.contributor.author | Harrington, K | |
dc.contributor.author | Kim, S-B | |
dc.contributor.author | Licitra, L | |
dc.contributor.author | Nixon, I | |
dc.contributor.author | Saba, NF | |
dc.contributor.author | Hackenberg, S | |
dc.contributor.author | Specenier, P | |
dc.contributor.author | Worden, F | |
dc.contributor.author | Balsara, B | |
dc.contributor.author | Leoni, M | |
dc.contributor.author | Martell, B | |
dc.contributor.author | Scholz, C | |
dc.contributor.author | Gualberto, A | |
dc.date.accessioned | 2021-04-13T10:17:26Z | |
dc.date.available | 2021-04-13T10:17:26Z | |
dc.date.issued | 2021-06-10 | |
dc.identifier.citation | Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2021, pp. JCO2002903 - ? | |
dc.identifier.issn | 0732-183X | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4518 | |
dc.identifier.eissn | 1527-7755 | |
dc.identifier.doi | 10.1200/jco.20.02903 | |
dc.description.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 (NCT02383927). | |
dc.format | Print-Electronic | |
dc.format.extent | JCO2002903 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | LIPPINCOTT WILLIAMS & WILKINS | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | |
dc.title | Tipifarnib in Head and Neck Squamous Cell Carcinoma With HRAS Mutations. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2021-03-22 | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1200/jco.20.02903 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | |
rioxxterms.licenseref.startdate | 2021-03-22 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | |
pubs.notes | Not 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-status | Published | |
pubs.embargo.terms | Not known | |
icr.researchteam | Targeted Therapy | |
icr.researchteam | Targeted Therapy | |
dc.contributor.icrauthor | Harrington, Kevin | |