ATIM-07. STUDY OF PEMBROLIZUMAB, TUMOR TREATMENT FIELDS (OPTUNE®) AND TEMOZOLOMIDE FOR OLDER SUBJECTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

Abstract

Given the median age of diagnosis in glioblastoma is 65 years, a sizable proportion of cases occur in the elderly population. One of the most feared complications of radiation in elderly patients is cognitive decline due to radiation-induced neurotoxicity, which can be irreversible, extremely debilitating and often progressive. Brandes et al. reported a worsening of neurologic status in 56% of 58 elderly patients 65 years of age or older treated with standard chemoradiation. In the elderly patient population, the use of radiation therapy can bring excessive toxicity, while the use of temozolomide alone leads to limited durability of efficacy. The addition of pembrolizumab and Optune might lead to prolonged survival without the need for upfront radiation therapy. Eligible participants include patients with newly-diagnosed glioblastoma age >= 65 years. This ongoing trial uses Optune continuously starting as soon as 4 weeks from surgery and continuing for up to 24 months. Temozolomide 150-200 mg/m2/day is dosed for 5 days every 28 days for up to 12 cycles and pembrolizumab 200 mg is dosed every 3 weeks for up to 24 months. The primary efficacy objective of this trial is to evaluate the potential anti-tumor activity of pembrolizumab in combination with Optune and temozolomide in newly diagnosed glioblastoma patients >= 65 years old. We will measure the percentage of patients who are alive at 12 months (OS12). Based on historical data showing an overall survival at 1-year of 20% in older glioblastoma patients, we set H0=20% and H1=45%. With 22 evaluable patients and a one-sided alpha of 0.05, the exact power is 85%. If at least 8 of 22 evaluable patients are alive at 1-year, this regimen will be considered for further study. Progression-free survival, objective response rate and duration of response for patients with measurable tumor will also be evaluated.