Chapter 7 156 A Single-Arm, Open-Label, Expanded Access Study of Vemurafenib in Patients With Metastatic Melanoma in the United States. Setup The expanded access program provided access to vemurafenib in 29 sites in the United States and data was prospectively collected after each treatment cycle of 28 days. After each cycle, patients returned to the treatment center for clinical assessment and new supply of the drug. The protocol, informed consent form, and accompanying patient information materials were approved by the institutional review board at each participating site before study initiation. Patients The expanded access program was open to patients with unresectable BRAF-v600 mutated positive metastatic melanoma. Of the 374 enrolled patients, 371 received treatment and were included in the safety analysis population. Patients had a median age of 53.5 years (range, 17-87). 109 patients had previously treated brain metastases (29%) and 59 (16%) and 12 (3%) patients had an ECOG performance status (PS) of 2 and 3 respectively. Outcome assessments were available for 241/371 patients. Interventions Patients received oral vemurafenib, a kinase inhibitor, 960 mg twice daily in cycles of 28 treatment days. Treatment was continued until disease progression, study termination by the sponsor following FDA approval of vemurafenib, death, or development of an intolerable adverse event. 135 patients completed at least 12 weeks of vemurafenib treatment, and 316 patients were receiving the full dosage of vemurafenib at the time of their last administration. Overall, 62 patients missed at least one dose because of AEs, and 42 patients required dose reductions because of AEs. Outcome The primary outcomes were objective response rate (ORR) as assessed by the physician, and the rates of treatment-related adverse events. The ORR was 54% (median time to response, 1.9 months). For patients with an ECOG PS of 0 or 1 (n = 210) and 2 or 3 (n = 31), the ORRs were 55%, and 42%, respectively. At least one treatment-related grade 3 AE was reported by 76 patients (21%), and six patients (2%) reported at least one treatment-related grade 4 AE.The most common treatment-related AEs were rash of any kind (37%), arthralgia (35%), photosensitivity reaction (26%), and fatigue (20%).
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