Improved Overall Survival With Addition of Chemotherapy to Radiation in Low-Grade Glioma
The addition of chemotherapy with procarbazine, lomustine, and vincristine to radiotherapy significantly prolonged overall survival in patients with low-grade glioma, according to the final results of the phase III RTOG 9802 trial reported in The New England Journal of Medicine by Buckner et al. A previous report from the trial showed significantly prolonged progression-free survival with the addition of chemotherapy.
Study Details
In the trial, 251 patients with grade 2 astrocytoma, oligoastrocytoma, or oligodendroglioma who were aged < 40 years and had undergone subtotal resection or biopsy or who were aged ≥ 40 years and had undergone biopsy or resection of any of the tumor were randomized between 1998 and 2002 to receive radiation therapy alone (n = 126) or followed by six cycles of combination chemotherapy with procarbazine, lomustine, and vincristine (n = 125). Radiotherapy was given at 54 Gy (30 fractions of 1.8 Gy) over 6 weeks. Chemotherapy was given as six 8-week cycles of oral procarbazine (60 mg/m2/d on days 8 to 21), oral lomustine (110 mg/m2 on day 1), and intravenous vincristine (1.4 mg/m2 on days 8 and 29).
For the chemotherapy and control groups, median age was 41 and 40 years; 52% and 61% were male; 89% and 92% were white; the extent of surgery was biopsy in 48% and 47%, partial resection in 41% and 44%, and total resection in 11% and 9%; histology was astrocytoma in 29% and 23%; oligodendroglioma in 40% and 45% and oligoastrocytoma in the remainder; and IDH1 R132H mutation was present in 64% and 61%, respectively.
Overall Survival
Median follow-up was 11.9 years, with 55% of patients having died. Median overall survival was 13.3 years among patients who received chemotherapy plus radiotherapy vs 7.8 years among those receiving radiotherapy alone (hazard ratio [HR] = 0.59, P = .003). Benefit was observed in subgroups with oligodendroglioma (HR = 0.43, P = .009), oligoastrocytoma (HR = 0.56, P = .05), astrocytoma (HR = 0.73, P = .31), and IDH1 mutation (HR = 0.42, P = .02). Overall survival was 72% vs 63% at 5 years and 60% vs 40% at 10 years.
Progression-Free Survival
Median progression-free survival was 10.4 vs 4.0 years (HR = 0.50, P < .001). Benefit was observed in subgroups with oligodendroglioma (HR = 0.36, P < .001), oligoastrocytoma (HR = 0.52, P = .02), astrocytoma (HR = 0.58, P = .06), and IDH1 mutation (HR = 0.32, P < .001). Progression-free survival was 61% vs 44% at 5 years and 51% vs 21% at 10 years.
Multivariate analysis showed that radiation therapy plus chemotherapy and oligodendroglioma histology were favorable prognostic factors for both progression-free and overall survival.
The investigators concluded: “In a cohort of patients with grade 2 glioma who were younger than 40 years of age and had undergone subtotal tumor resection or who were 40 years of age or older, progression-free survival and overall survival were longer among those who received combination chemotherapy in addition to radiation therapy than among those who received radiation therapy alone.
The study was funded by the National Cancer Institute and others.
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