Adjuvant temozolomide recommended for non-co-deleted anaplastic glioma
medwireNews: Adjuvant temozolomide chemotherapy significantly improves survival in patients with non-co-deleted anaplastic glioma, and should now be considered the standard of care in these patients, say the CATNON trial investigators.
Results from the planned interim analysis were so compelling that they were mandated for immediate release by the independent data monitoring committee, Martin van den Bent (Erasmus MC Cancer Institute, Rotterdam, the Netherlands) and team report in The Lancet.
The phase III CATNON (Concurrent and Adjuvant Temozolomide chemotherapy in non-1p/19q deleted) was conducted at 137 institutions in 12 European countries.
Patients with newly diagnosed non-co-deleted anaplastic glioma and WHO performance status scores of 0–2 were randomly assigned to receive radiotherapy alone (59.4 Gy in 33 fractions of 1.8 Gy; n=187) or with adjuvant temozolomide (150–200 mg/m2 on days 1–5 of 12 4-week cycles; n=185); or to receive radiotherapy with concurrent temozolomide (75 mg/m2 per day), with (n=188) or without (n=185) adjuvant temozolomide.
At the time of the planned interim analysis, after a median 27 months of follow-up, 344 (46%) of the 745 patients had disease progression and 221 (30%) had died.
The mortality rate was 25% among the 372 patients who received adjuvant temozolomide and 35% among the 373 patients who did not, with median overall survival (OS) time not reached in the former group versus 41.1 months in the latter.
After adjustment for performance status score, age, 1p loss of heterozygosity, presence of oligodendroglial elements, and MGMT promoter methylation status, patients who received adjuvant temozolomide had a significant 35% reduced risk for death compared with those who did not.
Disease progression was also significantly reduced with adjuvant temozolomide, at a median rate of 39%, compared with 54% in those who did not receive the drug in the adjuvant setting, while median progression-free survival (PFS) was 42.8 versus 19.0 months.
At 5 years, OS and PFS were 55.9% and 43.1%, respectively, with adjuvant temozolomide, and 44.1% and 24.3%, respectively, without it, but the researchers emphasize that follow-up is still immature.
“The data do not necessarily imply that concurrent temozolomide has no beneficial effect, but at the time of the interim analysis the survival values did not cross the predefined boundaries,” they write.
And although further studies “are needed to establish the efficacy of concurrent temozolomide chemotherapy, […] the [hazard ratios] for adjuvant temozolomide were striking and passed the very strict statistical boundaries of the preplanned interim analysis,” they add.
Van den Bent et al also point out that, in 2009, the discovery of mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2, which are associated with improved outcomes and “substantial metabolic differences” compared with non-mutated tumors, led them to amend the CATNON study protocol to screen for these genetic markers.
“Ongoing molecular research within this trial will show whether IDH1 and IDH2 mutational status and MGMT promoter methylation can be used to identify the patients who will benefit most from temozolomide chemotherapy,” the authors conclude.
By Laura Cowen
medwireNews is an independent medical news service provided by Springer Healthcare. © 2017 Springer Healthcare part of the Springer Nature group