The FDA independently reviewed an open-label, multicenter, noncomparative phase II study that randomly assigned 167 recurrent glioblastoma multiforme (GBM) patients to receive bevacizumab alone or bevacizumab in combination with irinotecan, although only efficacy data from the bevacizumab monotherapy arm (n = 85) were used to support drug approval. According to the FDA analysis of this study, tumor responses were observed in 26% of patients treated with bevacizumab alone, and the median duration of response in these patients was 4.2 months. On the basis of this externally controlled trial, the incidence of adverse events associated with bevacizumab did not appear to be significantly increased in GBM patients. The FDA independently assessed another single-arm, single-institution trial in which 56 recurrent glioblastoma patients were treated with bevacizumab alone. Responses were observed in 20% of patients, and the median duration of response was 3.9 months.
Currently, however, no data are available from prospective, randomized controlled trials demonstrating improvement in health outcomes, such as disease-related symptoms or increased survival with the use of bevacizumab to treat glioblastoma. On the basis of these data and FDA approval, bevacizumab monotherapy has become standard therapy for recurrent glioblastoma.
Systemic therapy (e.g., temozolomide, lomustine, or the combination of procarbazine, a nitrosourea, and vincristine in patients who have not previously received the drugs) has been used at the time of recurrence of primary malignant brain tumors. However, it has not been tested in controlled studies. Patient-selection factors likely play a strong role in determining outcomes, so the impact of therapy on survival is not clear.
Because there are no randomized trials, the role of repeat radiation after disease progression or the development of radiation-induced cancers is also ill defined. Interpretation is difficult because the literature is limited to small retrospective case series. The decision must be made carefully because of the risk of neurocognitive deficits and radiation necrosis.
Patients who have recurrent brain tumors are rarely curable and should be considered candidates for clinical trials when they have exhausted standard therapy. Information about ongoing clinical trials is available from the NCI Web site.