FDA Grants Bevacizumab Full Approval for Glioblastoma
Jason M. Broderick @jasoncology
Published Online: Tuesday, Dec 05, 2017
The FDA has granted bevacizumab (Avastin) a full approval for the treatment of adult patients with glioblastoma that progressed following prior therapy, according to Genentech, the manufacturer of the VEGF inhibitor.1
Bevacizumab previously received an accelerated approval in this setting. The conversion to a full approval is based on findings from the phase III EORTC 26101 study, in which adding bevacizumab to lomustine chemotherapy reduced the risk of disease progression or death by 48%.
“Glioblastoma is the most common and aggressive form of brain cancer and can be very difficult to treat,” Sandra Horning, MD, chief medical officer and head of Global Product Development at Genentech, said in a statement. “Delaying disease progression and reducing the need for corticosteroids over the course of treatment are considered important goals for those impacted by this devastating disease where patients have limited treatment options.”
The multicenter, randomized, open-label phase III EORTC 26101 study was conducted by the European Organization for Research and Treatment of Cancer. The study accrued 432 patients with recurrent glioblastoma.
Patients were randomized to bevacizumab plus lomustine chemotherapy versus lomustine alone. The primary endpoint was overall survival (OS). Progression-free survival (PFS) and overall response rate (ORR) were the main secondary outcome measures.
There was not a significant increase in OS with the addition of bevacizumab (HR, 0.91; P = 0.4578). However, adding bevacizumab to lomustine resulted in a median PFS of 4.2 months versus 1.5 months with lomustine alone (HR, 0.52; 95% CI, 0.41-0.64).
Half of the patients in the study were taking corticosteroids at baseline. Among these patients, 23% of patients in the bevacizumab arm were able to stop corticosteroids while on treatment, compared with 12% in the control arm.
Adverse events in the bevacizumab arm were similar to those observed in previous studies of the angiogenesis inhibitor across the tumor types of its approved indications. Adverse event–related discontinuations occurred in 22% of patients receiving the bevacizumab combination versus 10% of patients receiving chemotherapy alone.
The FDA granted bevacizumab an accelerated approval in May 2009 for use as a monotherapy to treat patients with glioblastoma who progressed on prior therapy. The approval was based on 2 single arm trials, AVF3708g and NCI 06-C-0064E.2
In the open, multicenter AVF3708g trial, previously treated patients with glioblastoma received 10 mg/kg IV of bevacizumab alone or combined with irinotecan every 2 weeks until disease progression or unacceptable toxicity. All patients had received prior temozolomide and radiotherapy.
The FDA only considered the single-agent arm for the accelerated approval. Among the 85 patients in this cohort, the ORR was 25.9% (95% CI, 17-36.1). The median response duration was 4.2 months (95% CI, 3.0-5.7).
In the single-arm NCI 06-C-0064E study, 56 patients with previously treated gliomas received 10 mg/kg IV of bevacizumab every 2 weeks until disease progression or unacceptable toxicity. All patients had prior temozolomide and radiation therapy.
The ORR was 19.6% (95% CI, 10.9-31.3). The median duration of response was 3.9 months (95% CI, 2.4-17.4).
In safety data from the AVF3708g study, the most common all-grade adverse events in the single-agent bevacizumab arm were infection, fatigue, headache, hypertension, epistaxis, and diarrhea. Adverse events led to discontinuation in 4.8% of patients receiving bevacizumab. There were 2 patient deaths (retroperitoneal hemorrhage and neutropenic infection) that investigators considered as potentially related to bevacizumab treatment.
Full article here.