Chemo-radiation promising for young glioma patients

6 Apr 2016

Younger adults with low-grade glioma lived more than 5 years longer if they received chemo-radiation rather than radiotherapy alone, long-term follow-up of a randomized trial showed.

Clinical trial details

The findings came from an updated analysis of the Radiation Therapy Oncology Group (RTOG) 9802 multicenter randomized trial involving patients with grade 2 gliomas, which account for 5% to 10% of primary brain tumors in adults. At the start of RTOG 9802, studies had produced evidence of tumor regression in patients with recurrent gliomas treated with various standard chemotherapy regimens.

RTOG 9802 involved adult patients younger than 40 with grade 2 astrocytoma, oligoastrocytoma, or oligodendroglioma, treated by subtotal resection or biopsy, or older patients who had undergone biopsy or resection of any tumor. Investigators randomized patients to radiation therapy alone or followed by six cycles of procarbazine-lomustine-vincristine chemotherapy. Overall survival was the primary endpoint.

Data analysis included 251 randomized patients. After a median follow-up of almost 12 years, the analysis of the results revealed that:

The 5.5-year difference in overall survival represented a 41% reduction in the survival hazard.
The chemo-radiation arm had a median 10-year progression-free of 51% versus 21% for patients who had radiation therapy alone (meaning a median overall survival of 13.3 years compared with 7.8 years for patients treated only with radiation).
The 10-year progression-free survival more than doubled with combination therapy, and 10-year overall survival improved by 50% (60% versus 40%)

Added toxicity with chemo-radiation

Treatment with both radiation and chemotherapy was one of only two favorable prognostic factors, the other being oligodendroglioma histology, Jan C. Buckner, MD, of the Mayo Clinic in Rochester, Minn., and colleagues reported. But the survival benefit came at a cost of added toxicity with chemo-radiation.

Although chemotherapy added toxicity, most toxic effects were grade 1/2 in severity, the authors reported. The most common toxicities were fatigue, anorexia, nausea, and vomiting. One patient in the combination arm developed neutropenic fever. No grade 5 toxicity occurred in either group.

"Although there appears to be a small cohort of patients with grade 2 glioma who do not benefit from radiation therapy plus chemotherapy, the identification of those patients remains elusive," the authors wrote. "The magnitude of treatment benefit from combined chemotherapy plus radiation therapy is substantial, but the toxic effects are greater than those observed with radiation therapy alone. Patients and their physicians will have to weigh whether the longer survival justifies the more toxic therapeutic approach."

The updated findings are consistent with reported outcomes

The results should help bring some clarity to the decision-making process for treating low-grade gliomas, according to Ajay Abad, MD, of Roswell Park Cancer Institute in Buffalo. The study also highlighted the importance of prognostic and predictive markers — including IDH-1, MGMT methylation status, and presence of the 1p/19q co-deletion — for classifying and risk-stratifying gliomas, as opposed to histologic subtype, Abad added.

The findings corroborated and extended those of an earlier analysis of the trial results, which showed an improvement in progression-free but not overall survival. A subgroup analysis showed a significant benefit with chemo-radiation among 2-year survivors, suggesting a delayed benefit of chemotherapy. The updated findings also are consistent with reported outcomes from recent updates of other phase 3 trials that demonstrated a survival advantage for chemo-radiation versus radiation therapy alone, the authors noted.

"The distributions for overall survival did not begin to show clear differences between the treatment groups until approximately 4 years after randomization, by which time approximately 25% of the patients had died," the authors noted. "Thereafter, the survival distributions continued to diverge in favor of the group that received radiation therapy plus chemotherapy."

An exploratory analysis showed that the survival benefit for combination therapy persisted across all histologic types but did not achieve statistical significance for astrocytoma. Another exploratory analysis showed improved survival among patients with IDH1 R132H mutations in their tumors, irrespective of treatment assignment. Nonetheless, radiation plus chemotherapy resulted in longer survival in the mutational subgroup as compared with radiation therapy alone.

Source: MedPage Today

Chemo-radiation promising for young glioma patients