Adjuvant Chemotherapy after Radiation Improved Overall Survival in Low-Grade Glioma

Adjuvant Chemotherapy after Radiation Improved Overall Survival in Low-Grade Glioma

Updated results of the Radiation Therapy Oncology Group (RTOG) 9802 trial confirmed that radiation therapy plus chemotherapy with procarbazine/CCNU/vincristine (PCV) improved overall survival (OS) and progression-free survival (PFS) in patients with low-grade gliomas compared with treatment with radiation therapy alone.

Jan C. Buckner, MD, of Mayo Clinic, presented the long-term results of RTOG 9802 (Abstract 2000) yesterday during the Oral Abstract Session “Central Nervous System Tumors.”

“Low-grade gliomas are not that common, but they occur in young patients, and the disease is almost invariably fatal,” Dr. Buckner said in an interview with ASCO Daily News. “Patients who receive radiation for low-grade glioma have an increased life expectancy of 5.5 years if they also receive PCV chemotherapy.”

RTOG 9802 randomly assigned 251 patients with diffuse grade 2 gliomas to radiation therapy alone or radiation therapy plus six cycles of PCV chemotherapy. The study included patients age 40 or older with any extent of resection and patients age 18 or older whose tumors were less than completely resected. (Patients younger than age 40 whose tumors were completely resected were considered low-risk and assigned to observation.)

Initial results of RTOG 9802 were published in the Journal of Clinical Oncology in 2012 (Shaw EG, et al. J Clin Oncol. 2012;30:3065-70). At that time, with a median follow-up of 5.9 years, the analysis showed that patients assigned to combination treatment had a significantly prolonged PFS compared with patients assigned to radiation alone. OS was not significantly prolonged in the interim analysis.

The updated results have a median follow-up of 11.9 years and 55% of patients have died, resulting in substantially greater statistical power, according to Dr. Buckner.

The data published in 2012 showed that radiation plus PCV significantly improved PFS with a hazard ratio (HR) of 0.6 (logrank p = 0.005; Wilcoxon p = 0.06). With further follow-up, the magnitude of benefit of PCV has become even more evident. The HR is now 0.5 in favor of radiation therapy plus PCV (logrank p < 0.001; Wilcoxon p = 0.002). The median PFS for patients assigned radiation therapy alone was 4 years compared with 10.4 years for patients undergoing combination treatment.

“This difference not only persists over time, but actually increases over time, with an absolute difference at 5 years of 17% increasing to nearly 30% at 10 years,” Dr. Buckner said.

The long-term results showed the difference in OS between the two arms is now statistically significant (HR 0.59; logrank p = 0.002; Wilcoxon p = 0.03). Patients treated with radiation therapy and PCV had a median OS of 13.3 years compared with 7.8 years for radiation alone. At 5 years, patients assigned the combination had an absolute survival benefit of approximately 10%, increasing to 20% by 10 years.

Dr. Buckner told ASCO Daily News that PCV has fallen out of favor recently with the use of temozolomide. He noted, however, that “we now have two studies that show that PCV substantially prolongs survival, and we do not have any studies that show that temozolomide prolongs survival.”

In addition, there are no direct comparison of temozolomide and PCV; there is an ongoing international study to address that question, Dr. Buckner said.

Martin J. van den Bent, MD, of Erasmus MC Cancer Institute, the Netherlands, was the invited discussant of what he called a practice-changing abstract.

“In 2014, we can safely conclude that we have established the role of chemotherapy in all diffuse glioma,” Dr. van den Bent said.