Phase II trial of bevacizumab and temozolomide for treatment of elderly patients with newly diagnosed glioblastoma.

2540 Background: Glioblastoma (GBM) in elderly patients differ molecularly as compared to younger patients, and may have increased angiogenic activity. Bevacizumab (BV) is an anti-angiogenic monoclonal antibody against vascular endothelial growth factor. We conducted a clinical trial to evaluate the efficacy and safety of BV and temozolomide (TMZ) for elderly patients with a new diagnosis of GBM, while deferring radiotherapy. Methods: This is a phase II, single-arm, multicenter, open label trial. Eligible patients have a tissue diagnosis of GBM with no treatment other than surgery, age ≥ 70, KPS ≥ 60, and adequate organ function. TMZ was initiated within 2 weeks of surgery and BV was initiated within 4 weeks thereafter. TMZ was administered at 150-200 mg/m 2 /day for 5 days every 4 weeks and BV at 10mg/kg every 2 weeks. A historical control group of 42 patients with similar criteria who received concurrent TMZ and RT followed by adjuvant TMZ, was derived for comparison from an institutional patient database. The primary endpoint is overall survival (OS) and secondary endpoints are progression-free-survival and safety. Results: 50 patients were enrolled from June 2010 to January 2016. Median age is 75 (range 70-87), and median KPS is 80 (range 60-100). 17 patients had a biopsy only, 26 patients have MGMT promoter methylation, and all patients are IDH wildtype. The study and control group are well matched in terms of age and molecular markers, however, the study patients had worse initial KPS and higher baseline tumor volume. At time of analysis, all but 2 patients were deceased. The median OS was 12.6 months for study patients (95% CI, 10.9-15.9 months) and 16.3 months for control patients (95% CI, 12.9-22.4 months). In a multivariate Cox analysis, baseline tumor volume (HR = 2.6, p = 0.0001) and MGMT promoter methylation (HR = 0.49, p = 0.004) were significant prognostic markers. Treatment type did not have a significant impact on OS (HR = 1.5, p = 0.14). Treatment-related serious adverse events included: pulmonary embolism (5), cerebral hemorrhage (3), pneumonia (1), intestinal perforation (1), deep venous thrombosis (6), hypertension (2), atrial fibrillation (1), congestive heart failure (1), cardio-respiratory arrest (1), lymphopenia (2), thrombocytopenia (8), and neutropenia (5). Conclusions: The results of this study suggest for patients with newly diagnosed GBM age ≥70 and KPS ≥60, treatment with BV and TMZ is equivalent to standard chemoradiotherapy, and has tolerable side effects. Complete endpoint analysis will be presented with the poster. Clinical trial information: NCT01149850 .