ACTR-78. TAMIGA: A PHASE II STUDY EVALUATING THE EFFICACY AND SAFETY OF CONTINUOUS BEVACIZUMAB THROUGH MULTIPLE LINES OF TREATMENT FOR GLIOBLASTOMA

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Bevacizumab (anti-vascular endothelial growth factor) prolongs progression-free survival (PFS) in newly diagnosed and recurrent glioblastoma. We hypothesized overall-survival (OS) benefit from continuing bevacizumab (BEV) through multiple lines of treatment (TML). Patients with newly diagnosed glioblastoma were enrolled in a multicenter, double-blind, placebo-controlled, randomized study (TAMIGA/NCT01860638). First-line (1L) treatment was radiotherapy plus temozolomide and BEV with maintenance treatment consisting of temozolomide plus BEV (six cycles) and BEV monotherapy until first disease progression (PD1). After PD1, patients were randomized to receive lomustine (CCNU) plus BEV or CCNU + placebo (P) until PD2. After PD2, patients received BEV plus chemotherapy (investigator choice; CIC) or P+CIC. Primary endpoint: OS. Secondary endpoints: PFS, OS rates, and safety. Overall, 296 patients were enrolled and 123 patients (due to withdrawal) were randomized at PD1 (BEV+CCNU, n=61; P+CCNU, n=62). After PD2, 25 patients in each arm received third-line treatment. Baseline characteristics were generally balanced. At randomization, 32.8% and 30.6% of the patients were receiving corticosteroids for BEV and placebo, respectively. The study terminated prematurely, due to the high withdrawal rate, implying underpowered (i.e. power=60%) inferential testing. For BEV versus placebo, respectively: median OS from randomization was 6.4 vs 5.5 months (HR=1.04, 95% CI 0.69–1.59); 6-month OS rate was 49.2% vs 38.7%; median time to corticosteroid initiation during second-line treatment was 5.8 vs 5.4 months; 86% and 83% had an adverse event (AE); 19% and 15% had ≥1 treatment-related grade ≥3 AEs; 21% and 15% had AEs leading to discontinuation. The study was underpowered for analysis of the primary endpoint. Descriptive analyses suggest neither an improvement nor detriment with the addition of BEV TML, in recurrent glioblastoma. No new safety signals were observed.

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