التفاصيل البيبلوغرافية
| العنوان: |
A Retrospective Evaluation of Vemurafenib as Treatment for BRAF-Mutant Melanoma Brain Metastases. |
| المؤلفون: |
Harding, James J., Catalanotti, Federica, Munhoz, Rodrigo R., Cheng, Donavan T., Yaqubie, Amin, Kelly, Nicole, McDermott, Gregory C., Kersellius, Romona, Merghoub, Taha, Lacouture, Mario E., Carvajal, Richard D., Panageas, Katherine S., Berger, Michael F., Rosen, Neal, Solit, David B., Chapman, Paul B. |
| المصدر: |
Oncologist; 2015, Vol. 20 Issue 7, p789-797, 9p, 1 Diagram, 4 Charts, 2 Graphs |
| مصطلحات موضوعية: |
BRAIN tumor genetics, ENZYME inhibitors, BRAIN tumors, CONFIDENCE intervals, MELANOMA, METASTASIS, GENETIC mutation, RESEARCH funding, SURVIVAL analysis (Biometry), SURVIVAL, TREATMENT effectiveness, RETROSPECTIVE studies, DATA analysis software, DESCRIPTIVE statistics, SEQUENCE analysis, DISEASE complications, GENETICS |
| مصطلحات جغرافية: |
NEW York (State) |
| مستخلص: |
Background. RAF inhibitors are an effective therapy for patients with BRAF-mutant melanoma and brain metastasis. Efficacy data are derived from clinical studies enriched with physiologically fit patients; therefore, it is of interest to assess the real-world experience of vemurafenib in this population. Tumor-specific genetic variants that influence sensitivity to RAF kinase inhibitors also require investigation. Methods. Records of patients with BRAF-mutant melanoma and brain metastases who were treated with vemurafenib were reviewed. Clinical data were extracted to determine extracranial and intracranial objective response rates, progression-free survival (PFS), overall survival (OS), and safety. A bait-capture, next-generation sequencing assay was used to identify mutations in pretreatment tumors that could explain primary resistance to vemurafenib. Results. Among patients with intracranial disease treated with vemurafenib, 27 were included in survival analyses and 22 patients were assessable for response. The extracranial and intracranial objective response rates were 71% and 50%, respectively. Discordant responses were observed between extracranial and intracranial metastatic sites in 4 of 19 evaluable patients. Median PFS was 4.1 months (95% confidence interval [CI]: 2.6-7.9); median intracranial PFS was 4.6 months (95% CI: 2.7-7.9), median OS was 7.5 months (95% CI: 4.3-not reached), with a 30.4% 1-year OS rate. Outcomes were influenced by performance status. Vemurafenib was tolerable, although radiation-induced dermatitis occurred in some patients who received whole-brain radiotherapy. Adequate samples for next-generation sequencing analysis were available for seven patients. Melanomas categorized as "poorly sensitive" (≥20% tumor growth, new lesions, or ≤50% shrinkage for <4 months) harbored co-occurring mutations in genes predicted to activate the phosphatidylinositol 3-kinase-AKT (PI3K-AKT) pathway. Conclusion. Vemurafenib is highly active in BRAF-mutant melanoma brain metastases but has limited activity in patients with poor performance status. The safety and efficacy of concurrent radiotherapy and RAF inhibition requires careful clinical evaluation. Combination strategies blocking the MAPK and PI3K-AKT pathway may be warranted in a subset of patients. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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