Adding Temozolomide to Radiotherapy Improves Survival in Elderly Patients With Newly Diagnosed Glioblastoma

Adding Temozolomide to Radiotherapy Improves Survival in Elderly Patients With Newly Diagnosed Glioblastoma
Adding Temozolomide to Radiotherapy Improves Survival in Elderly Patients With Newly Diagnosed Glioblastoma

CHICAGO — The addition of temozolomide to standard short-course radiation therapy (RT) significantly improved both overall and progression-free survival in elderly patients with newly diagnosed glioblastoma, results from the first study to test this combination in this age group concluded in a plenary presentation at the American Society of Clinical Oncology (ASCO) 2016 Annual Meeting.1

 “These data build upon prior key randomized trials and establish this RT/temozolomide regimen as a new standard option,” said James R. Perry, MD, The Crolla Family Endowed Chair in Brain Tumour Research at the Odette Cancer and Sunnybrook Health Sciences Centres in Toronto, Ontario, Canada. “This survival advantage is conferred without a sacrifice in quality of life and with manageable chemotherapy-related toxicities.”

Adults age 65 years and older account for half of all patients with glioblastoma. Current best practice is surgical resection followed by 6 weeks of RT with concurrent oral temozolomide followed by adjuvant temozolomide, a regimen established in 2005.

This study asked the principal question: “Does addition of concurrent and adjuvant temozolomide confer a survival advantage in patients 65 years and older receiving standard hypofractionated short-course RT?”

Patients were randomly assigned to RT at 40 Gy in 15 fractions over 3 weeks (n = 281) or to RT plus concurrent temozolomide 75 mg/m2 orally daily, from the first to the last day of RT, followed 4 weeks after the last RT dose by adjuvant temozolomide 150-200 mg/m2 on days 1 to 5 of each 28-day cycle (n = 281), until disease progression to a maximum of 12 cycles.

The primary end point was overall survival; secondary end points included progression-free survival, adverse events, quality of life, and translational studies, including mandatory MGMT promoter status.

Baseline characteristics were similar between the two arms. Median age was 73 years; two-thirds were older than 70 years.

Treatment adherence was high, with no difference between arms; more than 97% of patients adhered to the 3 weeks of chemoradiation. Duration of RT was administered in both arms as planned, as was duration of concomitant temozolomide; the median number of temozolomide maintenance cycles was 5. A total of 40% of patients received other treatment at progression; this also did not differ between the arms.

Uncommon grade 3/4 toxicities included leukopenia, 10% in the RT alone arm vs 27% in the RT plus temozolomide arm; neutropenia, 0% vs 9%; and thrombocytopenia, 0% vs 11%, respectively.

Median overall survival was 7.6 months in the RT arm (95% CI, 7.0-8.4) and 9.3 months in the RT plus temozolomide arm (95% CI, 8.3-10.3; HR, 0.67; 95% CI, 0.56-0.80; P < .0001). RT plus temozolomide also significantly improved median progression-free survival, 5.3 months (95% CI, 4.6-6.2) vs 3.9 months (95% CI, 3.5-4.3) for the RT alone arm (HR, 0.50; 95% CI, 0.41-0.60; P < .0001).

The 1-year and 2-year survival rates were 37.8% and 10.4% with RT plus temozolomide vs 22.2% and 2.8% with RT alone.

The overall survival benefit was particularly evident in the 165 patients with MGMT promoter methylation, “where median survival is nearly doubled,” Dr. Perry said. This was 13.5 months (95% CI, 10.2-15.3) for the RT plus temozolomide arm vs 7.7 months (95% CI, 5.8-10.7) for the RT alone arm (HR, 0.53; 95% CI, 0.38-0.73; P < .0001). For progression-free survival, these data were also significant, a median of 7.9 months vs 3.9 months (P < .0001), respectively.

“Remarkably, clinical benefit was also observed in patients with unmethylated tumors, and these provide the strongest data to data for the use of temozolomide” in all elderly patients with glioblastoma, he said. Median overall survival was 10.0 months (95% CI, 8.3-10.7) for the RT plus temozolomide arm vs 7.9 months (95% CI, 6.9-10.0) for the RT alone arm (HR, 0.75; 95% CI, 0.56-1.01; P = .055), while for progression-free survival, it was 4.8 months vs 4.4 months (P = .12).

In this study, treatment was completed by nearly all patients despite potential issues with mobility, treatment access, and caregiver access, he said.

The international phase 3 trial was led by the Canadian Cancer Trials Group with collaboration from the European Organization for the Research and Treatment of Cancer and the Trans-Tasmin Radiation Oncology Group.

Reference

1. Perry JR, Laperriere N, O'Callaghan CJ, et al. A phase III randomized controlled trial of short-course radiotherapy with or without concomitant and adjuvant temozolomide in elderly patients with glioblastoma (CCTG CE.6, EORTC 26062-22061, TROG 08.02, NCT00482677). Plenary presentation at: ASCO 2016 Annual Meeting; June 3-7, 2016; Chicago, IL.

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