Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402

Abstract

Purpose: Anaplastic oligodendrogliomas, pure (AO) and mixed (anaplastic oligoastrocytoma [AOA]), are chemosensitive, especially if codeleted for 1p/19q, but whether patients live longer after chemoradiotherapy is unknown.

Patients and methods: Eligible patients with AO/AOA were randomly assigned to procarbazine, lomustine, and vincristine (PCV) plus radiotherapy (RT) versus RT alone. The primary end point was overall survival (OS).

Results: Two hundred ninety-one eligible patients were randomly assigned: 148 to PCV plus RT and 143 to RT. For the entire cohort, there was no difference in median survival by treatment (4.6 years for PCV plus RT v 4.7 years for RT; hazard ratio [HR] = 0.79; 95% CI, 0.60 to 1.04; P = .1). Patients with codeleted tumors lived longer than those with noncodeleted tumors (PCV plus RT: 14.7 v 2.6 years, HR = 0.36, 95% CI, 0.23 to 0.57, P < .001; RT: 7.3 v 2.7 years, HR = 0.40, 95% CI, 0.27 to 0.60, P < .001), and the median survival of those with codeleted tumors treated with PCV plus RT was twice that of patients receiving RT (14.7 v 7.3 years; HR = 0.59; 95% CI, 0.37 to 0.95; P = .03). For those with noncodeleted tumors, there was no difference in median survival by treatment arm (2.6 v 2.7 years; HR = 0.85; 95% CI, 0.58 to 1.23; P = .39). In Cox models that included codeletion status, the adjusted OS for all patients was prolonged by PCV plus RT (HR = 0.67; 95% CI, 0.50 to 0.91; P = .01).

Conclusion: For the subset of patients with 1p/19q codeleted AO/AOA, PCV plus RT may be an especially effective treatment, although this observation was derived from an unplanned analysis.

Trial registration: ClinicalTrials.gov NCT00002569.

Fig 1.

CONSORT diagram. PCV, procarbazine, lomustine, and vincristine; RT, radiotherapy.

Fig 2.

Kaplan-Meier estimates of overall survival by treatment group. The hazard ratio (HR) for survival of patients treated with procarbazine, lomustine, and vincristine (PCV) plus radiotherapy (RT) compared with RT alone was 0.79 (95% CI, 0.60 to 1.04; P = .1).

Fig 3.

Kaplan-Meier estimates of overall survival by genotype for procarbazine, lomustine, and vincristine plus radiotherapy arm. The hazard ratio (HR) for overall survival of patients with 1p/19q codeleted anaplastic oligodendroglioma (AO)/anaplastic oligoastrocytoma (AOA) compared with those with AO/AOA in whom one or neither allele was deleted was 0.36 (95% CI, 0.23 to 0.57; P < .001).

Fig 4.

Kaplan-Meier estimates of overall survival by genotype for radiotherapy arm. The hazard ratio (HR) for overall survival of patients with 1p/19q codeleted anaplastic oligodendroglioma (AO)/anaplastic oligoastrocytoma (AOA) compared with those with AO/AOA in whom one or neither allele was deleted was 0.40 (95% CI, 0.27 to 0.60; P < .001).

Fig 5.

Kaplan-Meier estimates of overall survival by treatment for patients with 1p/19q codeleted anaplastic oligodendroglioma (AO)/anaplastic oligoastrocytoma (AOA). The hazard ratio (HR) for overall survival of patients with codeleted AO/AOA treated with procarbazine, lomustine, and vincristine (PCV) plus radiotherapy (RT) compared with those treated with RT alone was 0.59 (95% CI, 0.37 to 0.95; P = .03).

Fig 6.

Kaplan-Meier estimates of overall survival by treatment for patients with anaplastic oligodendroglioma (AO)/anaplastic oligoastrocytoma (AOA) in whom one or neither allele (1p or 19q) was deleted. The hazard ratio (HR) for overall survival of those with noncodeleted AO/AOA treated with procarbazine, lomustine, and vincristine (PCV) plus radiotherapy (RT) compared with those treated with RT alone was 0.85 (95% CI, 0.58 to 1.23; P = .39).

Fig A1.

Kaplan-Meier estimates of progression-free survival by treatment group. HR, hazard ratio; PCV, procarbazine, lomustine, and vincristine; RT, radiotherapy.

Fig A2.

Kaplain-Meier estimates of progression-free survival by genotype for procarbazine, lomustine, and vincristine plus radiotherapy arm. HR, hazard ratio.

Fig A3.

Kaplan-Meier estimates by genotype for radiotherapy arm. HR, hazard ratio.

Fig A4.

Kaplan-Meier estimates of progression-free survival by treatment for patients with 1p/19q codeleted anaplastic oligodendroglioma/anaplastic oligoastrocytoma. HR, hazard ratio; PCV, procarbazine, lomustine, and vincristine; RT, radiotherapy.

Fig A5.

Kaplan-Meier estimates of progression-free survival for patients with anaplastic oligodendroglioma/anaplastic oligoastrocytoma in whom one or neither allele (1p or 19q) was deleted. HR, hazard ratio; PCV, procarbazine, lomustine, and vincristine; RT, radiotherapy.