Chemotherapy After Radiation Increases Survival for Low-Grade Glioma Patients

The combination of chemotherapy and radiation therapy resulted in longer overall survival than radiation alone in certain patients with grade 2 gliomas, according to long-term results from a randomized trial.

Grade 2 gliomas make up 5% to 10% of all primary brain tumors in adults. “Progressive neurologic symptoms eventually develop in nearly all patients, and nearly all patients die prematurely,” wrote study authors led by Jan C. Buckner, MD, of the Mayo Clinic in Rochester, Minnesota.

Earlier results from this trial showed a progression-free survival benefit with a combined radiation and chemotherapy regimen, but no overall survival benefit. The trial included 254 patients enrolled between 1998 and 2002; all had grade 2 astrocytoma, oligoastrocytoma, or oligodendroglioma and were either younger than 40 years of age and had undergone subtotal resection or biopsy, or were 40 years of age or older and had undergone biopsy or resection of any of the tumor.

Patients were randomized to either radiation alone or radiation followed by chemotherapy with procarbazine, lomustine, and vincristine. The results were published in the New England Journal of Medicine.

After a median follow-up period of 11.9 years, 55% of the patients enrolled had died. Those who received chemotherapy had a median overall survival of 13.3 years, compared with only 7.8 years for those who received radiation alone. This yielded a hazard ratio (HR) for death of 0.59 (95% CI, 0.42-0.83; P = .003). The largest effect was seen in the subset of patients with oligodendroglioma, with an HR of 0.43 (95% CI, 0.23-0.82; P = .009). For oligoastrocytoma, the HR was 0.56 (95% CI, 0.32-1.00; P = .05), and for astrocytoma it was 0.73 (95% CI, 0.40-1.34; P = .31).

Patients who harbored a tumoral IDH1 R132H mutation had significantly longer overall survival regardless of treatment, at 13.1 years compared to 5.1 years without the mutation. Those with the mutation who received chemotherapy and radiation also had better overall survival than those who received radiation alone (P = .02).

The survival curves between the two treatment groups only began to diverge approximately 4 years after randomization. The 5-year overall survival rate was 72% with chemotherapy and 63% with radiation alone; at 10 years, the rates were 60% and 40%, respectively.

Toxicity was more frequent and more severe in the group that received chemotherapy, but the authors wrote that grade 3 or 4 events were uncommon, with the exception of neutropenia, which occurred in more than half the chemotherapy patients.

“Although there appears to be a small cohort of patients with grade 2 glioma who do not benefit from radiation therapy plus chemotherapy, the identification of those patients remains elusive,” the authors concluded. “The magnitude of treatment benefit from combined chemotherapy plus radiation therapy is substantial.... Patients and their physicians will have to weigh whether the longer survival justifies the more toxic therapeutic approach.”