The addition of bevacizumab to lomustine for the treatment of patients with progressive glioblastoma did not result in a significant improvement in overall survival, according to results of the European Organisation for Research and Treatment of Cancer (EORTC) 26101 trial published in the New England Journal of Medicine.
The US Food and Drug Administration approval of lomustine plus bevacizumab for patients with progressive glioblastoma is based on uncontrolled data, according to Wolfgang Wick, MD, of the University of Heidelberg and German Cancer Research Center, and colleagues. Data from a phase II trial suggested that this combination therapy might improve overall survival compared with lomustine monotherapy.
“EORTC was unable to confirm the conclusion of phase II trials that the addition of bevacizumab to lomustine improves survival in patients with progressive glioblastoma,” the researchers wrote. “The effect on progression-free survival was not associated with an increase in overall survival, and combination therapy was associated with increased toxicity.”
In the trial, 437 patients with progression after chemoradiation were randomly assigned 2:1 to lomustine with (n = 288) or without bevacizumab (n = 149). The primary endpoint was overall survival.
The median number of 6-week treatment cycles was 3 for patients assigned the combination and 1 for lomustine monotherapy. With 329 overall survival events, treatment with combined lomustine and bevacizumab did not result in an overall survival advantage. The median overall survival for combination treatment was 9.1 months compared with 8.6 months for lomustine monotherapy (hazard ratio [HR] for death, 0.95; 95% CI, 0.74–1.21; P = .65).
Treatment with lomustine plus bevacizumab did result in a 2.7-month longer locally assessed progression-free survival compared with monotherapy. The median progression-free survival was 4.2 months for combination treatment compared with 1.5 months for monotherapy (HR for progression or death, 0.49; 95% CI, 0.39–0.61; P < .001).
Patients assigned to combination treatment also experienced more grade 3 to 5 adverse events compared with lomustine alone (63.6% vs 38.1%).
“Although important given the lack of overall survival benefit, the higher numbers of adverse effects should be assessed relative to the longer treatment period in the combination group,” the researchers noted.