Elderly Glioblastoma Patients Benefit From Temozolomide Chemoradiation

A combined modality approach improves survival in newly diagnosed glioblastoma patients over 65 years of age

medwireNews: Phase III trial results indicate that newly diagnosed elderly glioblastoma patients derive a significant survival advantage from the addition of temozolomide to hypofractionated radiotherapy.

The findings presented at the annual meeting of the American Society of Clinical Oncology in Chicago, Illinois, USA, shore up those of a recent database analysis, which suggested that the combination protocol could be considered in the elderly glioblastoma population.

The presenting author James Perry, from Sunnybrook Health Sciences Centre in Toronto, Ontario, Canada, explained that although radiotherapy with concomitant and adjuvant temozolomide is considered the standard of care for glioblastoma patients, the landmark trial on which this is based was restricted to patients aged 70 years and younger. Thus, the benefit of this combination regimen is uncertain in patients aged between 65 and 70 years and unknown for those older than 70 years, he said.

The current trial included 562 participants with a median age of 73 years (range 65–90 years) who were randomly assigned to receive radiotherapy at a dose of 40 Gy in 15 fractions over 3 weeks with or without concomitant temozolomide (75 mg/m2 daily) followed 4 weeks after radiotherapy completion by monthly adjuvant temozolomide (150–200 mg/m2 on days 1–5 of a 28-day cycle for up to 12 cycles).

Both median overall survival (OS) and progression-free survival were significantly improved in the chemoradiation arm compared with the radiotherapy alone arm, at 9.3 versus 7.6 months (hazard ratio [HR]=0.67) and 5.3 versus 3.9 months (HR=0.50), respectively.

The benefit of temozolomide addition was especially evident among patients positive for methylation of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene, said the presenter. In this subgroup, OS was “nearly doubled” in the temozolomide relative to the radiation alone group, at a median of 13.5 versus 7.7 months (HR=0.53), he reported.

The presenter added that they also saw a survival gain in MGMT-unmethylated participants, “perhaps to our surprise”. Median OS was 10.0 months for temozolomide-treated patients compared with 7.9 months, giving an HR of 0.75, which “just missed statistical significance”.

A higher proportion of patients in the combined modality arm versus the radiation alone arm experienced grade 3 and 4 haematological toxicities – specifically, the rates of lymphopenia (27 vs 10%), thrombocytopenia (11 vs 0%) and neutropenia (9 vs 0%) were higher in the temozolomide group. But James Perry told the press that the adverse events were “manageable”.

Of note, the survival advantage did not come at the cost of quality of life, as assessed by the EORTC QLQ-C30 and QLQ-BN20 questionnaires. The on-treatment changes in scores were comparable between groups for all functional domains, except for nausea and vomiting during the first week and constipation during all 3 weeks of concomitant temozolomide and radiotherapy, which affected dual modality-treated patients to a significantly greater extent.

The speaker concluded that “oncologists now have the evidence to consider radiation with temozolomide for newly diagnosed elderly patients with glioblastoma.”

Reference

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). J Clin Oncol 2016; 34 (suppl; abstr LBA2). 

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