As reported in The Lancet Oncology by van den Bent et al, the final analysis of the phase III CATNON trial has shown continued overall survival benefit with radiotherapy followed by 12 cycles of adjuvant temozolomide in patients with newly diagnosed 1p/19q non–co-deleted anaplastic gliomas; exploratory analysis showed benefit of adjuvant temozolomide among patients with IDH-mutant disease.
Study Details
In the open-label trial, 751 patients from sites in Australia, Europe, and North America were randomly assigned 1:1:1:1 between December 2007 and September 2015 to receive radiotherapy alone (59.4 Gy in 33 fractions), radiotherapy with concurrent oral temozolomide (75 mg/m² per day), radiotherapy with adjuvant oral temozolomide (12 4-week cycles of temozolomide at 150–200 mg/m² on days 1–5), or radiotherapy with both concurrent and adjuvant temozolomide. A total of 444 patients had IDH-mutant astrocytoma. The primary endpoint of the study was overall survival.
Key Findings
Median follow-up for overall survival in the intention-to-treat population was 10.9 years (interquartile range = 9.5–12.7 years). Adjuvant temozolomide was associated with improved overall survival vs no adjuvant temozolomide (hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.54–0.77); no significant benefit was observed with concurrent vs no concurrent temozolomide (HR = 0.91, 95% CI = 0.76–1.08).
In an exploratory analysis including patients with IDH-mutant tumors, concurrent temozolomide did not significantly improve overall survival vs no concurrent temozolomide (median = 9.7 vs 7.2 years, HR = 0.81, 95% CI = 0.63–1.04). However, for adjuvant vs no adjuvant temozolomide, median overall survival was 12.5 vs 6.0 years (HR = 0.54, 95% CI = 0.42–0.69). No benefit of either concurrent or adjuvant temozolomide was observed among patients with IDH wild-type tumors.
In additional exploratory analyses, methylation-based subtyping and some DNA alterations (eg, amplification of PDGFRA and CDK4, homozygous deletion of CDKN2A, and total copy number variation) were associated with worse outcomes; none were associated with benefit of temozolomide.
The investigators concluded: “Long-term follow-up confirms that radiotherapy followed by 12 cycles of adjuvant temozolomide without concurrent temozolomide during radiotherapy improves survival for individuals with aggressive IDH[-mutant] astrocytoma.”
Martin J. van den Bent, MD, of Brain Tumor Center, Erasmus MC Cancer Institute, Rotterdam, Netherlands, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by MSD. For full disclosures of the study authors, visit thelancet.com.
