Wen PY, et al. – Experts aimed at assessing cabozantinib in patients with recurrent or refractory glioblastoma (GBM; NCT00704288). In this study, cabozantinib showed evidence of clinical activity in patients with recurrent GBM naive to antiangiogenic therapy. However, the predefined statistical target for success was not met. Adverse events (AEs) were frequently managed with dose reductions, at the starting doses assessed.

Methods

• They initially enrolled patients at a starting dose of 140 mg/day.
• However, the starting dose was amended to 100 mg/day because of toxicity.
• In addition, treatment continued until disease progression or unacceptable toxicity.
• Objective response rate (ORR) assessed by an independent radiology facility using modified RANO criteria was the primary endpoint.
• Duration of response, 6-month and median progression-free survival (PFS), overall survival (OS), and safety were reported as additional endpoints.

Results

• ORR was 17.6% and 14.5% in the 140-mg/day and 100-mg/day groups, in 152 patients naive to prior antiangiogenic therapy.
• Moreover, it did not meet the predefined statistical target for success.
• 22.3% and 27.8% were the proportions of patients alive and progression-free at 6 months.
• In both groups, median PFS was 3.7 months.
• Furthermore, median OS was 7.7 months and 10.4 months.
• As per observations, 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.
• 61.8% and 72.0% experienced dose reductions due to Aes.
• Fatigue, diarrhea, and palmar-plantar erythrodysesthesia syndrome were common grade 3/4 AEs.