Thursday, 13 October 2016

Long term analysis of NOA-04 for anaplastic (grade 3) gliomas published today

This was a randomized phase 3 trial testing radiation therapy (followed by chemotherapy with PCV or TMZ at recurrence) versus chemotherapy (followed by radiation therapy at recurrence). Half the chemotherapy patients were randomized to PCV and the other half to temozolomide.

In this new update, patients are divided into three molecular groups:  CIMP negative, CIMP positive 1p/19q codeleted, and CIMP positive 1p/19q non-codeleleted.  CIMP positivity in this study is essentially another way of saying "IDH-mutant" as IDH mutation virtually always leads to the CpG Island Methylator Phenotype (CIMP).   The latter two subgroups correspond to molecular oligodendroglioma and molecular astrocytoma, respectively.

One of the more important findings in this study is that PCV was superior to TMZ in the molecular oligodendroglioma subgroup.  (This image shows progression-free survival, but the same trend was evident in time-to-treatment failure analysis and overall survival).

On the other hand, PCV and TMZ were more or less equivalent in efficacy for the molecular astrocytoma group (CIMP+ non-codel).

These findings support the use of the PCV regimen for molecular oligodendrogliomas, however it's still an open question whether the addition of vincristine (V) to procarbazine (P) and CCNU (C) adds any benefit.  Some retrospective evidence suggests that PC chemotherapy (without vincristine) is comparable in efficacy to PCV.

This study was published in the November 2016 edition of Neuro-Oncology, and the figures above are taken from the Supplementary figures.


  1. Very interesting results. Our hospital proposed PVC and we've been fighting with them to have temodal but now it seems they might have been right? Do you know if the people in this study had already had surgery btw?

    1. In the group treated with first-line chemotherapy, 35% had prior complete resection, 42% had prior partial resection, and 23% had prior biopsy only. Median time from surgery to the start of chemotherapy was 28 days.