In an analysis of the phase III CeTeG/NOA-09 trial reported in The Lancet Oncology, Weller et al found no clinically relevant differences in health-related quality of life or neurocognitive function in patients with newly diagnosed MGMT-methylated glioblastoma treated with lomustine/temozolomide vs temozolomide alone. However, the open-label trial showed a significant improvement in overall survival in patients treated with lomustine/temozolomide vs temozolomide alone.
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Study Details
In the multicenter trial, 129 randomly assigned patients began treatment and were included in the modified intent-to-treat population, consisting of 66 in the lomustine/temozolomide group and 63 in the temozolomide-alone group. Patients received standard radiotherapy and were randomly assigned between June 2011 and April 2014 to either six 6-week courses of oral lomustine (100 mg/m² on day 1) plus temozolomide (100–200 mg/m² on days 2–6) or standard oral temozolomide (75 mg/m² daily during radiotherapy) plus six 4-week courses of temozolomide (150–200 mg/m² on days 1–5, every 4 weeks).
Assessments included health-related quality of life using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core-30; neurocognitive function using the Mini Mental State Examination (MMSE); and a neurocognitive test battery (NOA-07), including Trail Making Test A and B, working memory tests, and tests for lexical (Controlled Oral Word Association [COWA]) and semantic verbal fluency. Clinically relevant differences were defined as ≥ 10 points for health-related quality of life and ≥ 3 points for MMSE scores.
Median follow-up durations were 19.4 months for health-related quality of life (global health), 15.3 months for MMSE, and 11.0 months for COWA.
Key Findings
No significant impairment was observed for any item of health-related quality of life in the lomustine/temozolomide group, with the difference between groups for global health being 0.30 points (95% confidence interval [CI] = –0.23 to 0.83, P = .26).
A significant difference favoring temozolomide alone was found for MMSE (difference = –0.11, 95% CI = –0.19 to –0.03, P = .0058), but the difference was not clinically relevant (1.76 of 30 points over 4 years).
No significant differences were found between the lomustine/temozolomide group vs temozolomide-alone group in any subtest of the neurocognitive test battery (eg, difference in COWA = 0.04, 95% CI = –0.01 to 0.09, P = .14).
“The absence of systematic and clinically relevant changes in health-related quality of life and neurocognitive function combined with the survival benefit of lomustine/temozolomide vs temozolomide alone suggests that a long-term net clinical benefit exists for patients with newly diagnosed glioblastoma with methylation of the MGMT promoter, and supports the use of lomustine/temozolomide as a treatment option for these patients.”— Weller et al
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The investigators concluded: “The absence of systematic and clinically relevant changes in health-related quality of life and neurocognitive function combined with the survival benefit of lomustine/temozolomide vs temozolomide alone suggests that a long-term net clinical benefit exists for patients with newly diagnosed glioblastoma with methylation of the MGMT promoter and supports the use of lomustine/temozolomide as a treatment option for these patients.”
Ulrich Herrlinger, MD, of the Department of Neurology and Center of Integrated Oncology, University Hospital Bonn, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by the German Federal Ministry of Education and Research. For full disclosures of the study authors, visit thelancet.com.
