Abstract
Background
Cabozantinib is a tyrosine kinase inhibitor with activity against VEGFR2 and MET that has demonstrated clinical activity in advanced solid tumors. This open-label, phase II trial evaluated cabozantinib in patients with recurrent or refractory glioblastoma (GBM; NCT00704288). Methods
Patients were initially enrolled at a starting dose of 140 mg/day, but the starting dose was amended to 100 mg/day because of toxicity. Treatment continued until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) assessed by an independent radiology facility using modified RANO criteria. Additional endpoints included duration of response, 6-month and median progression-free survival (PFS), overall survival (OS), and safety. Results
Among 152 patients naive to prior antiangiogenic therapy, ORR was 17.6% and 14.5% in the 140-mg/day and 100-mg/day groups, respectively, which did not meet the predefined statistical target for success. The proportions of patients alive and progression-free at 6 months were 22.3% and 27.8%, respectively. Median PFS was 3.7 months in both groups, and median OS was 7.7 months and 10.4 months, respectively. The incidence of grade 3/4 adverse events (AEs) was 79.4% and 84.7% in the 140-mg/day and 100-mg/day groups, respectively, and dose reductions due to AEs were experienced by 61.8% and 72.0%, respectively. Common grade 3/4 AEs included fatigue, diarrhea, and palmar-plantar erythrodysesthesia syndrome. Conclusions
Cabozantinib showed evidence of clinical activity in patients with recurrent GBM naive to antiangiogenic therapy, although the predefined statistical target for success was not met. At the starting doses assessed, AEs were frequently managed with dose reductions. Clinical Trials Registration Number
NCT00704288 (http://ift.tt/2vWrPPz)from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2wgn4D3
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