Temozolomide regimen extends survival for people with grade 2 gliomas

ByMatthew Shinkle

Fact checked byMindy Valcarcel, MS

Key takeaways:

Temozolomide with radiation therapy improved 5- and 10-year OS for patients with grade 2 gliomas.
The addition of temozolomide did not extend PFS.

The addition of temozolomide to radiation therapy prolonged OS for patients with both co-deleted and non-co-deleted grade 2 gliomas, according to study results.

These are the first data from a randomized phase 3 trial to show temozolomide improves long-term survival for this specific patient population.

“I was delighted when I saw the results. Positive phase 3 clinical trials in glioma are a rarity,” David Schiff, MD, co-director of University of Virginia’s Neuro-Oncology Center, told Healio. “While it’s tricky ... to compare results of different studies, the hazard ratio benefit we saw with temozolomide was quite similar to that seen with [procarbazine plus lomustine plus vincristine] in RTOG 9802. This provides reassurance to clinicians who would prefer their patients receive a better tolerated chemotherapy and simpler regimen.”

Prior studies demonstrated radiation therapy and temozolomide have anti-tumor activity for patients with low-grade gliomas. However, limited data exist about temozolomide’s effect on patients with grade 2 gliomas.

Schiff and colleagues conducted the randomized phase 3 ECOG-ACRIN E3F05 study to assess whether the addition of radiation to temozolomide improves outcomes for patients with grade 2 gliomas.

Researchers enrolled 172 patients (median age, 44; 54% men) with grade 2 gliomas who had not received prior radiation or chemotherapy. All trial participants were aged older than 40 years, had uncontrolled symptoms or seizures, or progressed after initial observation.

Researchers randomly assigned patients 1:1 to radiation dosed at 50.4 Gy in 28 fractions alone, or radiation plus concomitant temozolomide and 12 4-week cycles of post-radiation temozolomide.

PFS served as the primary endpoint.

OS, quality of life, cognition, severe toxicities and impact of co-deletion status served as secondary endpoints.

After median follow-up of 117 months, results showed longer OS in the temozolomide group (HR = 0.54; 95% CI, 0.31-0.95).

A higher percentage of patients who received temozolomide survived 5 years (78% vs. 70%) and 10 years (70% vs. 47%).

HRs for OS appeared comparable between patients with and without 1p/19q co-deleted tumors (O.56 vs 0.53).

PFS did not differ significantly (HR = 0.76; 95% CI, 0.44-1.28).

Grade 3 or higher toxicity occurred more frequently among patients assigned temozolomide, including thrombocytopenia (11%) and neutropenia (5%).

“At least two important analyses remain to be completed,” Schiff told Healio. “The first has to do with our improved understanding of the molecular development of low-grade gliomas, which has resulted in our classification system for tumors having been revised twice since the inception of our study. A relatively new technique called methylation profiling will allow us to interpret our results in accordance with our improved classification system, and help us ascertain which patients are most likely to benefit from temozolomide.

“The second has to do with patient functioning,” he added. “Although radiation has gotten much safer over time, there still is some potential long-term impact on quality of life and cognition in patients with glioma who receive radiation. We are tracking quality of life and cognitive function in the patients on this study. This will allow us to see if the addition of temozolomide has any impact — positive or negative — on functioning, and examine the course of quality of life and cognitive function over time prior to the tumor starting to grow again.”