Bevacizumab plus irinotecan in recurrent malignant glioma shows high overall survival in a multicenter retrospective pooled series of the Spanish Neuro-Oncology Research Group (GEINO)

Abstract

There is no 'standard of care' for recurrent malignant glioma (MG). Our aim is to confirm the efficacy and safety of bevacizumab 10 mg/kg plus irinotecan 125 mg/m² (or 340 mg/m² if enzyme-inducing antiepileptic drugs) every 2 weeks for a maximum of 1 year in a retrospective pooled series of patients with recurrent MG. The inclusion criteria were as follows: age 18 years and above, histology of MG, progression after radiation and temozolomide, Karnofsky performance status (KPS) of at least 60, and signed informed consent for bevacizumab compassionate use. Response was assessed by MRI using the Macdonald criteria and evaluation of the FLAIR sequence every 8 weeks. A total of 130 patients were enrolled; 72% had glioblastoma (GBM). The median age of the patients was 53 years (20-78); the median KPS was 80%; the median number of prior chemotherapy lines was 2 (1-5); the median interval between the diagnosis of MG and inclusion was 14.6 months (2-166); and the median number of bevacizumab infusions was 8 (1-39). The median follow-up duration was 7.2 months (1-47). The median overall survival (OS) was 8.8 months for GBM and 11.2 months for anaplastic glioma (AG). The median progression-free survival was 5.1 months for GBM and 4.6 months for AG. The response rate was 56% for GBM and 68% for AG. Neurological and KPS improvements were observed in 49 and 45% of patients. Only KPS less than 80% was associated with a worse significant response rate (odds ratio, 0.57; 95% confidence interval, 0.22-0.96). The most frequent grades 3-4 toxicities were asthenia (7%), diarrhea (6%), and thromboembolic events (5%). There were five toxic deaths (4%). Bevacizumab plus irinotecan in recurrent MG improves responses, progression-free survival, and OS compared with historical data. KPS of at least 80% was a predictive factor for response and OS.

Bevacizumab is an active agent for recurrent high-grade glioma, but do we need randomized controlled trials?

“…Finally, the safety profile of this combination was broadly consistent with published studies. Importantly, tumor hemorrhage occurred in only one (1%) patient and thromboembolic events occurred in seven (5%) patients, all of which resolved with anticoagulant therapy and discontinuation of treatment [13]. Hence, this study adds to an important and growing body of evidence in support of the use of bevacizumab in patients with recurrent HGG.…”

“…In the article that accompanies this editorial, Gil et al [13] report on a retrospective experience from The Spanish Neuro-Oncology Research Group (GEINO) of the combination of bevacizumab and irinotecan for recurrent HGG. This was a relatively large series of 130 patients, Karnofsky Performance Status (KPS) 60 or more and disease progression after prior radiation and temozolomide, in which 72% of patients had glioblastoma.…”

“…The current study by Gil and colleagues yielded several other important findings. Response rates were assessed using the rigorous MacDonald criteria and were excellent: 56% (95% CI, 44.7-67) for glioblastoma and 68% (95% CI, 49.5-82.6) for AG [13]. Improvements in neurological state and KPS were shown in 49.2 and 45.2%, respectively, of symptomatic patients receiving bevacizumab and irinotecan.…”

Efficacy and safety of bevacizumab for the treatment of glioblastoma

“…Common and significant adverse events of all grades that have been associated with BEV monotherapy for patients with recurrent GBM include fatigue (32-63%), headache (20-36.9%), hypertension (12.5-29.8%), hemorrhage (overall, 27.4%), thromboembolic event (8-12.5%), and proteinuria (2.1-10%) (25,27,29,30). In previous studies, the most common adverse events detected following treatment with a combination of BEV and cytotoxic agents were hemorrhage (overall, 17.6-40.5%), fatigue (11.4-75.9%), hypertension (3.5-26.6%), and diarrhea (74.7%) (23,25,(41)(42)(43)(44)(45).…”

Approval denied by the European Medicines Agency (EMA) for bevacizumab in the treatment of high-grade glioma recurrence: a good idea or a grave error?

“…There are wide differences in its use in Europe. Administration in >500 patients treated in Europe retrospectively confirmed its activity [11][12][13]. An EORTC trial (study 26101) will explore various schedules of administration of bevacizumab.…”