As reported in the Journal of Clinical Oncology by Christina I. Tsien, MD, and colleagues, the phase II NRG Oncology/RTOG1205 trial has shown improved progression-free—but not overall—survival with concurrent bevacizumab and reirradiation vs bevacizumab alone in patients with recurrent glioblastoma.

Christina I. Tsien, MD

Study Details

In the U.S. multicenter trial, 170 eligible patients with tumor progression ≥ 6 months from completion of prior chemoradiation were randomly assigned between December 2012 and April 2016 to receive repeat radiation therapy (RT) at 35 Gy in 10 fractions (three-dimensional conformal RT, intensity-modulated RT, or proton therapy) with concurrent bevacizumab at 10 mg/kg every 2 weeks (n = 86) or bevacizumab alone (n = 84). Treatment was continued until disease progression or unacceptable toxicity. The primary outcome measure was overall survival.

Survival Outcomes

Median follow-up among censored patients was 12.8 months (range = 0.03–52.8 months). Median overall survival was 10.1 months (80% confidence interval [CI] = 9.5–11.3 months) in the reirradiation/bevacizumab group vs 9.7 months (80% CI = 9.0–11.2 months) in the bevacizumab alone group (hazard ratio [HR] = 0.98, 80% CI = 0.79–1.23, P = .46).

Median progression-free survival was 7.1 vs 3.8 months (HR = 0.73, 95% CI = 0.53–1.0, P = .05), with 6-month rates of 54.3% (95% CI = 43.5%–65.1%) vs 29.1% (95% CI = 19.1%–39.1%, P = .001). A total of 13 patients in the bevacizumab group received reirradiation as salvage therapy.

Adverse Events

Grade ≥ 3 adverse events occurred in 44% of patients in the reirradiation/bevacizumab group vs 43% of those in the bevacizumab group, most commonly nervous system disorders (21% vs 14%).

A total of four patients (4.8%) in the reirradiation/bevacizumab group had treatment-related acute grade ≥ 3 central nervous system adverse events, with none having treatment-related delayed grade ≥ 3 events. Adverse events led to death in eight (9.6%) vs four (5.3%) patients. Death considered at least possibly related to treatment occurred in two patients in the reirradiation/bevacizumab group, due to intratumoral hemorrhage in one and death–not otherwise specified in the other.

The investigators concluded, “To our knowledge, NRG Oncology/RTOG1205 is the first prospective, randomized multi-institutional study to evaluate the safety and efficacy of [reirradiation] in recurrent glioblastoma using modern RT techniques. Overall, [reirradiation] was shown to be safe and well tolerated. Bevacizumab plus RT demonstrated a clinically meaningful improvement in progression-free survival, specifically the 6-month progression-free survival rate, but no difference in overall survival.”

Dr. Tsien, of Johns Hopkins School of Medicine, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.