ATCT-13BEVACIZUMAB, RADIATION THERAPY (RT) AND TEMOZOLOMIDE FOLLOWED BY BEVACIZUMAB AND TEMOZOLOMIDE WITH CONTINUATION OF BEVACIZUMAB BEYOND PROGRESSION: A PHASE II TRIAL

Abstract

BACKGROUND: The addition of bevacizumab to RT and temozolomide in newly diagnosed glioblastoma patients was evaluated in two multicenter phase III trials, RTOG0825 and AVAglio, and demonstrated a lack of statistically significant increased survival. In both studies, the majority of patients discontinued bevacizumab at the time of disease progression on bevacizumab. Given encouraging results in other diseases, we evaluated the safety and benefit of incorporating bevacizumab from the time of diagnosis and throughout multiple treatment lines. METHODS: Patients with new diagnosis of WHO grade IV malignant glioma were enrolled after surgical intervention. Patients were initiated on RT and temozolomide (75 mg/m2/day), with bevacizumab (10 mg/kg every 14 days beginning at least 28 days post-operatively). Following RT, patients initiated adjuvant 5-day temozolomide for up to 12 cycles. Bevacizumab was maintained during adjuvant temozolomide, at tumor progression and once patients came off chemotherapy (maintenance phase). RESULTS: All planned 68 patients were enrolled on study. Median age was 55 years and 69% were men. Of the 55 patients who have progressed, 37 (67%) received bevacizumab at progression. We observed a median progression- free survival of 9.8 months [95% confidence interval (CI), 8.8, 13.5 months) and median overall survival of 17.6 months (CI, 14-22.5 months). No study related death occurred. Study related grade 4 toxicities include: thrombocytopenia (n = 7); neutropenia (n = 5); leukopenia (n = 4); and one each of lymphopenia, colonic perforation, sepsis, intracranial hemorrhage, and hypertension. Grade 3 toxicities include: lymphopenia (n = 29); thrombocytopenia (n = 12); neutropenia (n = 10); leukopenia (n = 8); fatigue (n = 10); hypertension (n = 9); proteinuria (n = 6); thromboembolic event (n = 4); nausea (n = 3); acute coronary syndrome (n = 2); allergic reaction (n = 2); infection (n = 5); and one each of anemia, elevated ALT, ventricular tachycardia, optic nerve neuropathy, constipation, oral mucositis, pustular rash, wound infection, cognitive difficulties, stroke, and headaches. CONCLUSION: Continuing bevacizumab beyond progression is tolerable. Subgroup analyses of survival will be presented.