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Phase II Pilot Study of Vemurafenib in Patients With Metastatic BRAF-Mutated Colorectal Cancer.
Kopetz, Scott; Desai, Jayesh; Chan, Emily; Hecht, Joel Randolph; O'Dwyer, Peter J; Maru, Dipen; Morris, Van; Janku, Filip; Dasari, Arvind; Chung, Woonbook; Issa, Jean-Pierre J; Gibbs, Peter; James, Brian; Powis, Garth; Nolop, Keith B; Bhattacharya, Suman; Saltz, Leonard.
Afiliación
  • Kopetz S; Scott Kopetz, Dipen Maru, Van Morris, Filip Janku, and Arvind Dasari, The University of Texas MD Anderson Cancer Center, Houston, TX; Emily Chan, Vanderbilt-Ingram Cancer Center, Nashville, TN; Joel Randolph Hecht, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles
  • Desai J; Scott Kopetz, Dipen Maru, Van Morris, Filip Janku, and Arvind Dasari, The University of Texas MD Anderson Cancer Center, Houston, TX; Emily Chan, Vanderbilt-Ingram Cancer Center, Nashville, TN; Joel Randolph Hecht, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles
  • Chan E; Scott Kopetz, Dipen Maru, Van Morris, Filip Janku, and Arvind Dasari, The University of Texas MD Anderson Cancer Center, Houston, TX; Emily Chan, Vanderbilt-Ingram Cancer Center, Nashville, TN; Joel Randolph Hecht, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles
  • Hecht JR; Scott Kopetz, Dipen Maru, Van Morris, Filip Janku, and Arvind Dasari, The University of Texas MD Anderson Cancer Center, Houston, TX; Emily Chan, Vanderbilt-Ingram Cancer Center, Nashville, TN; Joel Randolph Hecht, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles
  • O'Dwyer PJ; Scott Kopetz, Dipen Maru, Van Morris, Filip Janku, and Arvind Dasari, The University of Texas MD Anderson Cancer Center, Houston, TX; Emily Chan, Vanderbilt-Ingram Cancer Center, Nashville, TN; Joel Randolph Hecht, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles
  • Maru D; Scott Kopetz, Dipen Maru, Van Morris, Filip Janku, and Arvind Dasari, The University of Texas MD Anderson Cancer Center, Houston, TX; Emily Chan, Vanderbilt-Ingram Cancer Center, Nashville, TN; Joel Randolph Hecht, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles
  • Morris V; Scott Kopetz, Dipen Maru, Van Morris, Filip Janku, and Arvind Dasari, The University of Texas MD Anderson Cancer Center, Houston, TX; Emily Chan, Vanderbilt-Ingram Cancer Center, Nashville, TN; Joel Randolph Hecht, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles
  • Janku F; Scott Kopetz, Dipen Maru, Van Morris, Filip Janku, and Arvind Dasari, The University of Texas MD Anderson Cancer Center, Houston, TX; Emily Chan, Vanderbilt-Ingram Cancer Center, Nashville, TN; Joel Randolph Hecht, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles
  • Dasari A; Scott Kopetz, Dipen Maru, Van Morris, Filip Janku, and Arvind Dasari, The University of Texas MD Anderson Cancer Center, Houston, TX; Emily Chan, Vanderbilt-Ingram Cancer Center, Nashville, TN; Joel Randolph Hecht, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles
  • Chung W; Scott Kopetz, Dipen Maru, Van Morris, Filip Janku, and Arvind Dasari, The University of Texas MD Anderson Cancer Center, Houston, TX; Emily Chan, Vanderbilt-Ingram Cancer Center, Nashville, TN; Joel Randolph Hecht, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles
  • Issa JP; Scott Kopetz, Dipen Maru, Van Morris, Filip Janku, and Arvind Dasari, The University of Texas MD Anderson Cancer Center, Houston, TX; Emily Chan, Vanderbilt-Ingram Cancer Center, Nashville, TN; Joel Randolph Hecht, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles
  • Gibbs P; Scott Kopetz, Dipen Maru, Van Morris, Filip Janku, and Arvind Dasari, The University of Texas MD Anderson Cancer Center, Houston, TX; Emily Chan, Vanderbilt-Ingram Cancer Center, Nashville, TN; Joel Randolph Hecht, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles
  • James B; Scott Kopetz, Dipen Maru, Van Morris, Filip Janku, and Arvind Dasari, The University of Texas MD Anderson Cancer Center, Houston, TX; Emily Chan, Vanderbilt-Ingram Cancer Center, Nashville, TN; Joel Randolph Hecht, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles
  • Powis G; Scott Kopetz, Dipen Maru, Van Morris, Filip Janku, and Arvind Dasari, The University of Texas MD Anderson Cancer Center, Houston, TX; Emily Chan, Vanderbilt-Ingram Cancer Center, Nashville, TN; Joel Randolph Hecht, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles
  • Nolop KB; Scott Kopetz, Dipen Maru, Van Morris, Filip Janku, and Arvind Dasari, The University of Texas MD Anderson Cancer Center, Houston, TX; Emily Chan, Vanderbilt-Ingram Cancer Center, Nashville, TN; Joel Randolph Hecht, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles
  • Bhattacharya S; Scott Kopetz, Dipen Maru, Van Morris, Filip Janku, and Arvind Dasari, The University of Texas MD Anderson Cancer Center, Houston, TX; Emily Chan, Vanderbilt-Ingram Cancer Center, Nashville, TN; Joel Randolph Hecht, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles
  • Saltz L; Scott Kopetz, Dipen Maru, Van Morris, Filip Janku, and Arvind Dasari, The University of Texas MD Anderson Cancer Center, Houston, TX; Emily Chan, Vanderbilt-Ingram Cancer Center, Nashville, TN; Joel Randolph Hecht, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles
J Clin Oncol ; 33(34): 4032-8, 2015 Dec 01.
Article en En | MEDLINE | ID: mdl-26460303
PURPOSE: BRAF V600E mutation is seen in 5% to 8% of patients with metastatic colorectal cancer (CRC) and is associated with poor prognosis. Vemurafenib, an oral BRAF V600 inhibitor, has pronounced activity in patients with metastatic melanoma, but its activity in patients with BRAF V600E-positive metastatic CRC was unknown. PATIENTS AND METHODS: In this multi-institutional, open-label study, patients with metastatic CRC with BRAF V600 mutations were recruited to an expansion cohort at the previously determined maximum-tolerated dose of 960 mg orally twice a day. RESULTS: Twenty-one patients were enrolled, of whom 20 had received at least one prior metastatic chemotherapy regimen. Grade 3 toxicities included keratoacanthomas, rash, fatigue, and arthralgia. Of the 21 patients treated, one patient had a confirmed partial response (5%; 95% CI, 1% to 24%) and seven other patients had stable disease by RECIST criteria. Median progression-free survival was 2.1 months. Patterns of concurrent mutations, microsatellite instability status, CpG island methylation status, PTEN loss, EGFR expression, and copy number alterations were not associated with clinical benefit. In contrast to prior expectations, concurrent KRAS and NRAS mutations were detected at low allele frequency in a subset of the patients' tumors (median, 0.21% allele frequency) and were apparent mechanisms of acquired resistance in vemurafenib-sensitive patient-derived xenograft models. CONCLUSION: In marked contrast to the results seen in patients with BRAF V600E-mutant melanoma, single-agent vemurafenib did not show meaningful clinical activity in patients with BRAF V600E mutant CRC. Combination strategies are now under development and may be informed by the presence of intratumor heterogeneity of KRAS and NRAS mutations.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Cutáneas / Sulfonamidas / Carcinoma de Células Escamosas / Neoplasias Colorrectales / Proteínas Proto-Oncogénicas B-raf / Indoles / Mutación Tipo de estudio: Clinical_trials / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: J Clin Oncol Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Cutáneas / Sulfonamidas / Carcinoma de Células Escamosas / Neoplasias Colorrectales / Proteínas Proto-Oncogénicas B-raf / Indoles / Mutación Tipo de estudio: Clinical_trials / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: J Clin Oncol Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos