A single-arm, open-label, expanded access study of vemurafenib in patients with metastatic melanoma in the United States
| Autor: | Lee D. Cranmer, Sigrun Hallmeyer, Rene Gonzalez, Anna C. Pavlick, John D. Hainsworth, F. Stephen Hodi, Lynn M. Schuchter, Bann Mo Day, C. Lance Cowey, David F. McDermott, David H. Lawson, R. Linke, Fred J. Kudrik, Brendan D. Curti, Paul B. Chapman, Kim Margolin, Keith T. Flaherty, Omid Hamid, Gerald P. Linette, Antoni Ribas, Lawrence E. Flaherty |
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| Rok vydání: | 2014 |
| Předmět: |
Oncology
Male Cancer Research Skin Neoplasms Indoles medicine.medical_treatment neoplasm metastasis/drug therapy Melanoma/drug therapy Neoplasm Metastasis Vemurafenib Melanoma Cancer education.field_of_study Sulfonamides clinical trial Middle Aged brain neoplasms/drug therapy melanoma/genetics Female Patient Safety medicine.drug medicine.medical_specialty Population Clinical Trials and Supportive Activities Oncology and Carcinogenesis Ipilimumab QT interval Clinical Research Internal medicine medicine BRAF protein Humans human Oncology & Carcinogenesis education Adverse effect brain neoplasms/secondary business.industry Neurosciences vemurafenib/adverse effects medicine.disease vemurafenib/therapeutic use Dermatology United States Clinical trial Radiation therapy business |
| Zdroj: | Cancer journal (Sudbury, Mass.), vol 20, iss 1 |
| Popis: | Purpose This open-label, multicenter study was designed to allow access to vemurafenib for patients with metastatic melanoma, bridging the time between end of enrollment in the phase III registration trial (December 2010) and commercial availability following US Food and Drug Administration approval of vemurafenib for the treatment of unresectable or metastatic BRAF-mutated melanoma (August 2011). Patients and methods Eligible patients had metastatic melanoma with a BRAF mutation (detected by the cobas 4800 BRAF V600 Mutation Test). Unlike previous vemurafenib trials, patients with poor performance status (PS) and treated brain metastases were permitted. Enrolled patients received oral vemurafenib 960 mg twice daily. Results Of 374 patients enrolled at 29 US sites (December 2010 to October 2011), 371 patients received vemurafenib and were followed up for a median of 2.8 months (the study had a prespecified end upon vemurafenib approval and commercial availability). At baseline, most patients (75%) had stage M1c disease, and 19% had an Eastern Cooperative Oncology Group PS of 2 or 3; 72% of patients had received prior systemic therapy for metastatic melanoma, 27% received prior ipilimumab, and 29% radiotherapy for prior brain metastases. Because reassessment data to confirm response were not available for most patients, point estimates of objective response rate (ORR) are reported. Among 241 efficacy-evaluable patients, the ORR was 54% (median time to response, 1.9 months). The ORR in non-central nervous system sites in patients with previously treated brain metastases (n = 68) was 53%. The ORR in prior ipilimumab-treated patients (n = 68) was 52%. For patients with PS of 0 or 1 (n = 210) and 2 or 3 (n = 31), the ORRs were 55%, and 42%, respectively. The safety profile observed was consistent with that reported in previous studies. The number of patients with grade 3 or 4 treatment-related adverse events was higher in patients with PS 2 or 3 than in those with PS 0 or 1 (10% vs. 5%, respectively). Adverse events requiring a dose reduction (at least 1 level) occurred in 11% of patients, and 9 patients (2%) experienced events leading to vemurafenib withdrawal, including 2 with repeated QT interval prolongation. Discussion This study confirmed the established rapid and high tumor response rate achievable with vemurafenib in BRAF mutation-positive metastatic melanoma. Several groups not included in previous studies, including patients with previously treated brain metastases, Eastern Cooperative Oncology Group PS 2 to 3, or previous ipilimumab treatment had benefitted from vemurafenib similar to the overall population. No new safety signals were detected. |
| Databáze: | OpenAIRE |
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