Phase II trial for patients with newly diagnosed glioblastoma (GBM) treated with carmustine wafers followed by concurrent radiation therapy (RT), temozolomide (TMZ), and bevacizumab (BV), then followed by TMZ and BV post-RT.

Abstract

e13015^ Background: Standard treatment for GBM includes RT and TMZ, followed by six cycles of TMZ, for a median overall survival (OS) and progression-free survival (PFS) of 14.6 and 6.9 months, respectively. BV is FDA approved for recurrent GBM and carmustine wafers are approved for newly diagnosed and recurrent GBM. We evaluated the safety and efficacy of carmustine wafers insertion followed by concurrent RT, TMZ and BV, followed by TMZ and BV for newly diagnosed GBM patients. Methods: Treatment consisted of: Part A- carmustine wafers insertion at resection followed by RT and TMZ at 75 mg/m2/day. BV at 10 mg/kg every two weeks started at least 28 days post-operatively. Part B- Patients received 12 cycles of TMZ (200 mg/m2on days 1-5 of a 28-day cycle) and BV every two weeks (day 1 and 15). Results: Forty one patients of a planned accrual of 72 were enrolled. The study was closed early due to six grade 4-5 toxicities related to study intervention, which met the safety criteria to discontinue the trial. Three patients had grade 4 cerebral edema and one each had grade 4 fatigue, wound infection and meningitis. Median age was 56 years (range, 27-77 years) and 28 patients were men. Of 41 patients, 36 completed part A and 31 started part B. Eleven patients are still on study and 4 have completed part B. Twenty six patients are off study due to progression (n = 16), adverse events (n = 8) and consent withdrawal (n = 2). At a median follow-up of 12.6 months (95% CI: 10.8-15.6 months) the median PFS is 11.3 months (95% CI: 9.2-12.9 months) and the median OS is 16.1 months (95% CI: 15.8 months- ∞). Grade 3-5 toxicities so far include: thrombocytopenia (grade 3, n = 2; grade 4, n = 2), stroke (grade 3, n = 1; grade 5, n = 1), infection (grade 3, n = 2), meningitis (grade 3, n = 1; grade 4, n=1), venous thromboembolic events (grade 3, n = 5), cerebral edema (grade 4, n = 3), fatigue (grade 4, n = 1), enterocolitis (grade 3, n = 1), and wound infection (grade 3, n = 2; grade 4, n = 1). Conclusions: For the patients who did well post carmustine wafers insertion, the treatment was tolerable and median PFS and OS has improved. Updated survival and toxicity results will be presented. Clinical trial information: NT01186406.