Combination of bevacizumab plus irinotecan in recurrent malignant gliomas (MG): A retrospective study of efficacy and safety

Abstract

13011 Background: Recurrent MG have poor prognosis and low response rates to available treatments. Following data from Vredenburg´s phase II trial (pro ASCO 2005) some centres began to treat recurrent MG with bevacizumab and irinotecan. The aim of this study is to confirm efficacy and safety of this combination in non-selected consecutive patients (pts). Methods: Data from 6 Spanish hospitals was collected retrospectively. All pts were > 18 years, had to sign an informed consent and to present: histological documented MG; progression after radiation and temozolomide; measurable disease on MRI; have received at least 3 infusions of treatment schedule: Irinotecan 125mg/m2 and bevacizumab 10 mg/kg every 2 weeks for a maximum of a year. Response rate (RR) was determinate by MRI (performed every 6 cycles) using McDonald criteria. Progression free survival (PFS) and overall survival (OS) were calculated by Kaplan Meier method. Results: From August 2006 to October 2007, 44 consecutive pts (28 Glioblastoma, 11 Anaplastic Astrocitoma & 5 Anaplastic Oligoastrocitoma) were treated with this combination. Median age: 53 years (25–73). Median number of prior chemotherapy: 2 (1–4). Six cases had received irinotecan previously. Median KPS: 70% (60–100). Median Barthel Index: 100% (55–100). 26 pts received dexamethasone with median dosage: 4 mg (1–18). 29 were taking a non enzyme-inducing antiepileptic drug. Median cycles received: 9 (4–23) Toxicity grade 3–4: Asthenia in 6 pts; thrombocytopenia 1; neutropenia 1; mucositis 2 pts; thomboembolic complications (TEC) 3 pts, skin 1, haemorrhage out of CNS 2 pts and severe cognitive impairment 4 cases. Efficacy: 25 pts had response (4 complete response); 12 pts stable disease ≥ 3 months and 7 progression as best response. RR was 56.8% (95% CI [41–71.6]) Mean follow-up: 5.8 months (1.6–16.2). Mean PFS was 7.4 months (4,6–10,1). OS was 9.8 months (6.8–12.8). Conclusion: Our experience suggests that the combination of bevacizumab plus irinotecan in recurrent MG improves the RR, PFS and OS when compared with historical figures. However, this regimen is not free of severe toxicity (TEC and severe cognitive impairment) and requires a careful selection of patients. A phase 3 trials to validate this combination is needed. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche