Trial Outcomes for Newly Diagnosed Anaplastic Oligodendroglioma & Oligoastrocytoma

by Stephen Western
Astrocytoma Options.com

EORTC 26951 and RTOG 9402

Two different randomized phase III trials testing PCV chemotherapy for anaplastic (grade III) oligodendroglioma or oligoastrocytoma published results in the June 2006 edition of the Journal of Clinical Oncology (1, 2). The European EORTC 26951 trial recruited patients between the years 1996 and 2002, and the North American RTOG 9402 trial recruited patients between 1994 and 2002. The trials were similar except for a few differences: EORTC 26951 patients in the experimental arm received radiation therapy prior to PCV chemotherapy, and all were required to have 3 of 5 anaplastic characteristics for eligibility; patients in the experimental arm of RTOG 9402 received PCV prior to radiation therapy, received increased doses of CCNU and procarbazine compared to the EORTC 26951 trial, and all patients were required to have only 2 of 5 anaplastic characteristics for eligibility.

Both of these trials have published long-term analyses including outcomes based on molecular data such as IDH1 mutation (3). The most revealing of these updates was published online in February 2014 in the Journal of Clinical Oncology (4). This was an updated analysis of RTOG 9402 which compared outcomes in both the RT arm and the PCV plus RT arm subdivided into three different subgroups: patients with IDH mutation and 1p/19q codeletion; patients with IDH mutation, without 1p/19q codeletion; and patients with neither IDH mutation nor 1p/19q codeletion. Outcomes for these 3 subgroups receiving either RT alone or PCV followed by RT are as follows.

Of patients with anaplastic oligodendroglioma or oligoastrocytoma with both IDH mutation and 1p/19q codeletion, 46 received radiation therapy alone and had a median survival of 6.8 years, while 42 patients received PCV chemotherapy followed by radiation and had a median survival of 14.7 years. This improved survival with early PCV chemotherapy was highly significant, with a p-value of 0.01.

Of patients with IDH mutation, but without 1p/19q codeletion, 29 received radiation alone and had a median survival of 3.3 years, while 37 patients received PCV chemotherapy followed by radiation and had a median survival of 5.5 years. This improved survival with early PCV chemotherapy was statistically significant, with a p-value of 0.045.

Of patients with neither IDH mutation nor 1p/19q codeletion, 18 received radiation alone and had a median survival of 1.3 years, while 26 patients received PCV chemotherapy followed by radiation and had a median survival of 1 year. The difference in median survival in this case was insignificant, with a p-value of 0.97. Most of the patients in the radiation-only arm received chemotherapy at the time of recurrence. Though early PCV chemotherapy did not improve overall survival in patients without IDH mutation-1p/19q codeletion, it is possible that the patients in the radiation-only arm benefited from chemotherapy received at the time of tumour recurrence (without salvage chemotherapy, their median survival may have been significantly less).

These outcomes suggest that anaplastic oligodendroglioma/oligoastrocytoma patients with IDH mutations, with or without 1p/19q codeletion, benefit from early PCV chemotherapy. This may also have relevance for IDH-mutated astrocytoma. On the other hand, anaplastic oligodendroglioma/oligoastrocytoma patients without IDH mutation may not benefit significantly from early PCV chemotherapy, but this does not rule out a possible benefit from later salvage chemotherapy.

Both of these phase III trials initiated and completed patient recruitment prior to the establishment of temozolomide as the new standard of care drug for malignant gliomas. Whether or not these findings are also relevant to TMZ chemotherapy is a question that awaits publication of the ongoing CATNON (for non-1p/19q codeleted anaplastic gliomas) and CODEL (for 1p/19q codeleted anaplastic glioma). Preliminary data should be forthcoming within the next few years.

References

1. Adjuvant Procarbazine, Lomustine, and Vincristine Improves Progression-Free Survival but Not Overall Survival in Newly Diagnosed Anaplastic Oligodendrogliomas and Oligoastrocytomas: A Randomized European Organisation for Research and Treatment of Cancer Phase III Trial. van den Bent et al. 2006.
   READ SOURCE DOCUMENT (PDF)


2. Phase III Trial of Chemotherapy Plus Radiotherapy Compared With Radiotherapy Alone for Pure and Mixed Anaplastic Oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402. Cairncross et al. 2006.
   READ SOURCE DOCUMENT (PDF)


3. Adjuvant Procarbazine, Lomustine, and Vincristine Chemotherapy in Newly Diagnosed Anaplastic Oligodendroglioma: Long-Term Follow-Up of EORTC Brain Tumor Group Study 26951. van den Bent et al. 2012.
   READ SOURCE DOCUMENT (PDF)


4. Benefit From Procarbazine, Lomustine, and Vincristine in Oligodendroglial Tumors Is Associated With Mutation of IDH. Cairncross et al. 2014.
   READ ABSTRACT

This page was created on 04/14/2014 and last updated on 04/21/2019