Table 3.
Efficacy and safety analyses from EXIST-1 and EXIST-2
| Trial | Efficacy | Safety |
|---|---|---|
| EXIST-136 | Primary end point | • AEs were mostly grade 1/2 in severity |
| • TSC patients (n = 117) with ≥ 1 SEGA ≥ 1 cm and either serial growth of SEGA, a new lesion of ≥ 1 cm, or new or worsening hydrocephalus | • SEGA response rate: 35% vs 0% (EVE vs PBO; P < 0.0001) | |
| Key secondary end points | • Most common AEs were mouth ulceration (32% vs 5% EVE vs PBO), stomatitis (31% vs 21% EVE vs PBO), convulsions (23% vs 26% EVE vs PBO), and pyrexia (22% vs 15% EVE vs PBO) | |
| • Change from baseline to week 24 in the total number of seizures per 24 hours | ||
| • Oral 4.5 mg/m2/day everolimus titrated to target whole blood trough level of 5–15 ng/mL | – No significant difference in seizure frequency was found in the everolimus arm relative to placebo (P = 0.20) | |
| • Time to progression of SEGA | ||
| – No EVE patients progressed vs six PBO patients (15.4%) (P = 0.0002) | ||
| • Skin lesion response rate (among patients with ≥ 1 skin lesion at baseline; n = 110) | ||
| – 42% vs 11% (EVE vs PBO; P = 0.0004) | ||
| Exploratory end points | ||
| • Angiomyolipoma response rate (among patients with ≥ 1 angiomyolipoma ≥ 1 cm in longest diameter at baseline; n = 44) 53% vs 0% (EVE vs PBO) | ||
| EXIST-260 | Primary end point | • AEs were mostly grade 1/2 in severity |
| • TSC or sporadic lymphangioleiomyomatosis patients (n = 118) with ≥ 1 angiomyolipoma ≥3 cm in longest diameter, no requirement for angiomyolipoma-related surgery, or no angiomyolipoma-related bleeding or embolization in past 6 months | • Angiomyolipoma response rate | |
| – 42% vs 0% (EVE vs PBO; P < 0.0001) Key secondary end points | • Most common AEs were stomatitis (48% vs 8% EVE vs PBO), nasopharyngitis (24% vs 31% EVE vs PBO), and acne-like skin lesions (22% vs 5% EVE vs PBO) | |
| Key secondary end points | ||
| • Time to progression of angiomyolipoma | ||
| – EVE was superior to PBO (hazard ratio: 0.08; 95% CI: 0.02–0.37; P < 0.0001) | ||
| • Oral 10 mg/day EVE | • Skin lesion response rate (among patients with ≥ 1 skin lesion at baseline; n = 114): 26% vs 0% (EVE vs PBO; P = 0.0002) |
Abbreviations: AE, adverse event; CI, confidence interval; EVE, everolimus; EXIST, EXamining everolimus In a Study of TSC; PBO, placebo; SEGA, subependymal giant cell astrocytoma; TSC, tuberous sclerosis complex; vs, versus.