10001-ACT-1 A MULTICENTER EXPLORATORY PHASE II STUDY OF NEOADJUVANT BEVACIZUMAB FOR NEWLY DIAGNOSED MALIGNANT GLIOMA - THE SECOND REPORT

Abstract

Abstract BACKGROUND Preoperative bevacizumab (Bev) is a standard treatment strategy for colorectal cancers, but not malignant gliomas. This multi-institutional phase I/II study was conducted to confirm the safety and explore the clinical utility of preoperative Bev for newly diagnosed glioblastoma (GB). METHODS Patients were enrolled based on magnetic resonance imaging (MRI) findings typically suggestive of GB. Preoperative Bev and temozolomide (TMZ) were administered at doses of 10 mg/kg on day 0 and 150 mg/m2 on days 1-5, respectively. Surgical resection was performed between days 21 and 30, inclusive. The initial safety evaluation was performed for the initial 7 cases and efficacy was evaluated in a total of 15 cases by progression-free survival (PFS), changes in tumor volume, Karnofsky Performance Scale (KPS) and Mini-Mental State Examination (MMSE) scores after preoperative therapy. RESULTS The study protocol was judged as acceptable. Tumor resection was performed on a mean of day 23.7. Pathological diagnosis was GB, isocitrate dehydrogenase (IDH)-wildtype in 14 cases and GB, IDH-mutant in 1 case, according to the WHO 2016 criteria. Severe adverse events possibly related to preoperative Bev and TMZ were observed in 2 of the 15 patients, as wound infection and postoperative hematoma and thrombocytopenia. KPS and MMSE scores were significantly improved with preoperative therapy. Tumor volume was decreased in all but one case on T1-weighted imaging with contrast-enhancement (T1CE) and in all cases on fluid-attenuated inversion recovery, with mean volume decrease rates of 36.2% and 54.0%, respectively. Tumor volume decrease rate on T1CE and PFS tended to correlate. Median PFS and overall survival were 9.5 months and 16.5 months, respectively. CONCLUSIONS Preoperative Bev and TMZ is confirmed to be safe. The strategy might be useful for GB in some patients, not only reducing tumor burden, but also improving patient KPS preoperatively.