Joint Final Report of EORTC 26951 and RTOG 9402: Phase III Trials With Procarbazine, Lomustine, and Vincristine Chemotherapy for Anaplastic Oligodendroglial Tumors

Abstract

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the basis of the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Anaplastic oligodendroglial tumors (AOTs) are chemotherapy-sensitive brain tumors. We report the final very long-term survival results from European Organization for the Research and Treatment of Cancer 26951 and Radiation Therapy Oncology Group 9402 phase III trials initiated in 1990s, which both studied radiotherapy with/without neo/adjuvant procarbazine, lomustine, and vincristine (PCV) for newly diagnosed anaplastic oligodendroglial tumors. The median follow-up duration in both was 18-19 years. For European Organization for the Research and Treatment of Cancer 26951, median, 14-year, and probable 20-year overall survival rates without versus with PCV were 2.6 years, 13.4%, and 10.1% versus 3.5 years, 25.1%, and 16.8% (N = 368 overall; hazard ratio [HR] 0.78; 95% CI, 0.63 to 0.98; P = .033), with 1p19q codeletion 9.3 years, 26.2%, and 13.6% versus 14.2 years, 51.0%, and 37.1% (n = 80; HR 0.60; 95% CI, 0.35 to 1.03; P = .063), respectively. For Radiation Therapy Oncology Group 9402, analogous results were 4.8 years, 16.5%, and 11.2% versus 4.8 years, 29.1%, and 24.6% (N = 289 overall; HR 0.79; 95% CI, 0.61 to 1.03; P = .08), with codeletion 7.3 years, 25.0%, and 14.9% versus 13.2 years, 46.1%, and 37% (n = 125; HR 0.61; 95% CI, 0.40 to 0.94; P = .02), respectively. With that, the studies show similar long-term survival even without tumor recurrence in a significant proportion of patients after first-line treatment with radiotherapy/PCV.

Trial registration: ClinicalTrials.gov NCT00002569 NCT00002840.

FIG 1.

OS and PFS in the intent-to-treat populations. (A) OS by treatment arm in EORTC 26951, intent-to-treat population. (B) PFS by treatment arm in EORTC 26951, intent-to-treat population. (C) OS by treatment arm in RTOG 9402, intent-to-treat population. (D) PFS by treatment arm in RTOG 9402, intent-to-treat population. EORTC, European Organization for the Research and Treatment of Cancer; OS, overall survival; PCV, procarbazine, lomustine, and vincristine; PFS, progression-free survival; RT, radiotherapy; RTOG, Radiation Therapy Oncology Group.

FIG 2.

OS and PFS in the patients with 1p/19q codeleted tumors. (A) OS by treatment arm among 1p/19q codeleted cases in EORTC 26951, assessed with FISH. (B) PFS by treatment among 1p/19q codeleted cases in EORTC 26951 (FISH). (C) OS by treatment arm among 1p/19q codeleted cases in RTOG 9402. (D) PFS by treatment arm among 1p/19q codeleted cases in RTOG 9402. EORTC, European Organization for the Research and Treatment of Cancer; FISH, fluorescent in situ hybridization; OS, overall survival; PCV, procarbazine, lomustine, and vincristine; PFS, progression-free survival; RT, radiotherapy; RTOG, Radiation Therapy Oncology Group.