95% CI (30.8, 53.4) (0.0, 9.0)
There were 3 patients in the AFINITOR arm and 8 patients in the placebo arm with documented angiomyolipoma progression by central radiologic review. The time to angiomyolipoma progression was statistically significantly longer in the AFINITOR arm (HR 0.08 [95% CI: 0.02, 0.37]; p <0.0001).
Skin lesion response rates were assessed by local investigators in 77 patients in the AFINITOR arm and 37 patients in the placebo arm with skin lesions at study entry. The skin lesion response rate was statistically significantly higher in the AFINITOR arm (26% versus 0, p=0.0011); all skin lesion responses were partial responses, defined as visual improvement in 50%-99% skin lesions, considering all skin lesions, durable for at least 8 weeks (Physician's Global Assessment of Clinical Condition).
14.5 Subependymal Giant Cell Astrocytoma with Tuberous Sclerosis Complex
Study 1 was a randomized (2:1), double-blind, placebo-controlled trial of AFINITOR Tablets conducted in 117 pediatric and adult patients with subependymal giant cell astrocytoma (SEGA) and tuberous sclerosis complex (TSC). Eligible patients had at least one SEGA lesion ≥ 1.0 cm in longest diameter on MRI based on local radiology assessment and one or more of the following: serial radiological evidence of SEGA growth, a new SEGA lesion ≥ 1 cm in longest diameter, or new or worsening hydrocephalus. Patients randomized to the treatment arm received AFINITOR Tablets at a starting dose of 4.5 mg/m2 daily, with subsequent dose adjustments as needed to achieve and maintain everolimus trough concentrations of 5 to 15 ng/mL as tolerated. AFINITOR/matched placebo treatment continued until disease progression or unacceptable toxicity. MRI scans for disease assessment were obtained at baseline, 12, 24, and 48 weeks, and annually thereafter.
The main efficacy outcome measure was SEGA response rate based on independent central radiology review. SEGA response was defined as a ≥ 50% reduction in the sum of SEGA volume relative to baseline, in the absence of unequivocal worsening of non-target SEGA lesions, a new SEGA lesion ≥ 1 cm, and new or worsening hydrocephalus. Analysis of SEGA response rate was limited to the blinded treatment period which ended 6 months after the last patient was randomized. The analysis of SEGA response rate was stratified by use of enzyme-inducing antiepileptic drugs (EIAEDs) at randomization (yes versus no).
Of the 117 patients enrolled, 78 were randomized to AFINITOR and 39 to placebo. The median age was 9.5 years (range 0.8 to 26 years; 69% were 3 to < 18 years at enrollment; 17% were < 3 years at enrollment), 57% were male, and 93% were Caucasian. At baseline, 18% of patients were receiving EIAEDs. Based on central radiology review at baseline, 98% of patients had at least one SEGA lesion ≥ 1.0 cm in longest diameter, 79% had bilateral SEGAs, 43% had ≥ 2 target SEGA lesions, 26% had growth in or into the inferior surface of the ventricle, 9% had evidence of growth beyond the subependymal tissue adjacent to the ventricle, and 7% had radiographic evidence of hydrocephalus. The median values for the sum of all target SEGA lesions at baseline were 1.63 cm3 (range 0.18 to 25.15 cm3) and 1.30 cm3 (range 0.32 to 9.75 cm3) in the AFINITOR and placebo arms respectively. Eight (7%) patients had prior SEGA-related surgery. The median duration of follow-up was 8.4 months (range 4.6 to 17.2 months).
The SEGA res |
