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Tipifarnib in Head and Neck Squamous Cell Carcinoma With HRAS Mutations.
Ho, Alan L; Brana, Irene; Haddad, Robert; Bauman, Jessica; Bible, Keith; Oosting, Sjoukje; Wong, Deborah J; Ahn, Myung-Ju; Boni, Valentina; Even, Caroline; Fayette, Jerome; Flor, Maria José; Harrington, Kevin; Kim, Sung-Bae; Licitra, Lisa; Nixon, Ioanna; Saba, Nabil F; Hackenberg, Stephan; Specenier, Pol; Worden, Francis; Balsara, Binaifer; Leoni, Mollie; Martell, Bridget; Scholz, Catherine; Gualberto, Antonio.
Afiliación
  • Ho AL; Memorial Sloan Kettering Cancer Center, New York, NY.
  • Brana I; Department of Medicine, Weill Cornell Medical College, New York City, NY.
  • Haddad R; Vall D'Hebron Institute of Oncology, Barcelona, Spain.
  • Bauman J; Dana-Farber Cancer Institute, Boston, MA.
  • Bible K; Fox Chase Cancer Center, Philadelphia, PA.
  • Oosting S; Mayo Clinic, Rochester, MN.
  • Wong DJ; University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Ahn MJ; UCLA Medical Center, Los Angeles, CA.
  • Boni V; Samsung Medical Center, Seoul, Korea.
  • Even C; START Madrid-CIOCC, Madrid, Spain.
  • Fayette J; Gustave Roussy, Villejuif, France.
  • Flor MJ; Centre Leon Berard, Lyon, France.
  • Harrington K; Hospital Virgen del Rocio, Sevilla, Spain.
  • Kim SB; The Institute of Cancer Research, London, England.
  • Licitra L; Asan Medical Center, Seoul, Korea.
  • Nixon I; Fondazione IRCCS Istituto Nazionale Tumori Milano and University of Milan, Italy.
  • Saba NF; Beatson West of Scotland Cancer Centre, Glasgow, Scotland.
  • Hackenberg S; Winship Cancer Institute of Emory University, Atlanta, GA.
  • Specenier P; Universitätsklinikum Würzburg, ENT Department and Early Clinical Trial Unit, Würzburg, Germany.
  • Worden F; University Hospital Antwerp, Edegem, Belgium.
  • Balsara B; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI.
  • Leoni M; Kura Oncology, Boston, MA.
  • Martell B; Kura Oncology, Boston, MA.
  • Scholz C; Kura Oncology, Boston, MA.
  • Gualberto A; Kura Oncology, Boston, MA.
J Clin Oncol ; 39(17): 1856-1864, 2021 06 10.
Article en En | MEDLINE | ID: mdl-33750196
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).
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Proto-Oncogénicas p21(ras) / Quinolonas / Mutación Missense / Carcinoma de Células Escamosas de Cabeza y Cuello / Neoplasias de Cabeza y Cuello Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: J Clin Oncol Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Proto-Oncogénicas p21(ras) / Quinolonas / Mutación Missense / Carcinoma de Células Escamosas de Cabeza y Cuello / Neoplasias de Cabeza y Cuello Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: J Clin Oncol Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos