Long-term results from the Radiation Therapy Oncology Group (RTOG) 9802 study in high-risk grade 2 gliomas were presented at the 2014 ASCO Annual Meeting. The study’s mature analysis showed a 41% reduction in mortality at 5 years with combination radiation therapy followed by six cycles of PCV chemotherapy (procarbazine [Matulane], lomustine [CeeNU], and vincristine).

While grade 2 gliomas are relatively indolent, nearly all patients eventually develop progressive neurologic symptoms and die from their disease. This is the first prospective study to show a treatment-related survival benefit.

 “For patients with grade 2 glioma, with less than gross total tumor resection or who are more than 40 years of age, radiotherapy plus PCV prolongs both progression-free and overall survival, compared to radiotherapy alone,” reported Jan C. Buckner, MD, of the Mayo Clinic, Rochester, Minnesota.

Study Details

In the RTOG 9802 trial, 251 patients with diffuse grade 2 gliomas were randomly assigned to radiation therapy alone (54 Gy in 30 fractions) or to radiation therapy followed by six cycles of PCV. At a median follow-up of almost 12 years, median progression-free survival was 10.4 years with the combination vs 4.0 years with radiotherapy alone, a 50% reduction in risk (P < .001 by log-rank test).

Median overall survival was 13.3 years with the combination vs 7.8 years with radiotherapy alone (P = .002 by log-rank test). The 5-year overall survival rate was also better with the combination (72.3% vs 63.1%), as was the 10-year overall survival rate (60.1% vs 40.1%).

“Median survival was increased by 5.5 years, and 5-year and 10-year survival was increased by 9% and 20%, respectively,” he said.

 “With further follow-up and more events [55% of patients had died], the difference in overall survival is now statistically significant,” Dr. Buckner reported. The mature findings confirm earlier analyses of a progression-free survival benefit, and add statistical significance to the survival improvement. In the earlier analysis, deaths were reduced by 28%, but this was not statistically significant.

The study also identified treatment with PCV, oligodendroglioma histology, and female gender as favorable prognostic variables.

Hematologic toxicity was greater with the combination, but only a few patients required red cell or platelet transfusion.

“Toxicity was greater with PCV but is acceptable and similar to that seen with many combination chemotherapy regimens commonly in use,” Dr. Buckner noted. “Severe cognitive impairment at 5 years, measured by the Mini-Mental State Exam, was infrequent and, compared with baseline, improvement was somewhat more likely than decline.”

Longer-term or less-severe cognitive decline could not be assessed, he added. Future analyses will assess treatment effect by histologic type, by molecular markers, and by germline polymorphisms. ■

Disclosure: Dr. Buckner reported no potential conflicts of interest. For full disclosures of all study authors visit meetinglibrary.asco.org.

Reference

1. Buckner JC, Pugh SL, Shaw EG, et al: Phase III study of radiation therapy with or without procarbazine, CCNU, and vincristine in low-grade glioma: RTOG 9802 with Alliance, ECOG, and SWOG. ASCO Annual Meeting. Abstract 2000. Presented June 2, 2014.