Long-Term Survival Possible With Vincristine Plus Radiotherapy in Anaplastic Oligodendroglial Tumors

Disease control and survival lengthen when adding procarbazine, lomustine, and vincristine (PCV) chemotherapy to radiation therapy (RT) compared to RT alone as a first-line therapy following surgery in patients with anaplastic oligodendroglial tumors. Such results aid the PCV’s importance as a therapeutic chemotherapy regimen for gliomas and with temozolomide (Temodar) because of its lower toxicity and beneficial efficacy.¹

The findings are from joint results from the NRG/Radiation Therapy Oncology Group (NCT00002569) and European Organization for the Research and Treatment of Cancer 26951 clinical trial (NCT00002840) published in the Journal of Clinical Oncology. The studies suggest the possibility of long-term survival in a significant proportion of patients with a 1p/19q co-deleted oligodendroglioma.²

To be considered eligible, patients must have had anaplastic oligodendroglioma or anaplastic oligo-astrocytoma, had not undergone radiotherapy or chemotherapy and had adequate marrow, liver, and renal function. The EORTC study randomized 368 eligible patients to receive RT with or without PCV after RT for 6 cycles. The RTOG trial randomized 289 eligible patients to receive RT or 4 cycles of intensified PCV before RT.

After roughly 20 years of median follow-up in both trials, the overall survival (OS) in the EORTC study was 57%, 51%, and 37% for patients with chromosome 1p19q co-deleted tumors who were randomized to receive PCV-chemoradiotherapy at 10, 15, and 20 years, respectively vs 43%, 26%, and 14%, respectively, for patients who received RT alone. The RTOG study showed OS rates of 57%, 46%, and 37% in patients who received PCV and RT vs 32%, 25%, and 15% for patients who received RT alone. Additionally, patients with IDH-mutant non-co-deleted tumors who underwent PCV, and RT showed longer progression-free survival and OS than patients who received only RT in both studies.

“Both studies demonstrated a 40% reduction in the risk of death (HR 0.59 RTOG, 0.60 EORTC) by adding neo/adjuvant PCV to RT in 1p19q co-deleted anaplastic oligodendroglial tumors, with median survival of [about] 14 years (13.2 RTOG, 14.2 EORTC). Even more remarkably, in this extremely long-term and mature analysis, 20 years after diagnosis, approximately 30% of patients with a co-deleted tumor remained progression-free and nearly 40% were still alive following PCV-chemoradiotherapy,” explained Andrew B. Lassman, MD, chief of neuro-oncology at Columbia University Vagelos College of Physicians and Surgeons, Herbert Irving and New York-Presbyterian Hospital, New York, NY, and the lead author of the NRG/RTOG 9402 EORTC manuscript in a press release.

“These trials, initiated nearly 30 years ago under the visionary leadership of Dr. Gregory Cairncross (RTOG), Martin van den Bent (EORTC), and colleagues, transformed our understanding of the clinical behavior of molecularly defined gliomas and contributed to the classification of gliomas used globally today. Importantly, these extremely long-term results also show that early PCV can be associated with durable disease control and survival, especially among patients with 1p19q co-deleted tumors,” Lassman added.

The report stressed that both trials were funded by government, allowing for a much longer survival results and allowing for longer follow-ups to achieve full maturity. Such time frames are very difficult and nearly impossible to replicate with a commercial sponsor, according to authors of the joint report.²

_REFERENCE:

_{1. Joint final report of phase iii trials demonstrate positive outcomes from combination of PCV chemotherapy and RT in patients with anaplastic oligodendroglial tumors. Press release. NRG Oncology. June 28, 2022. Accessed June 29, 2022. https://bit.ly/3nszAIw}

_{2. Lassman AB, Hoang-Xuan K, Polley MC, et al. Joint Final report of EORTC 26951 and RTOG 9402: phase iii trials with procarbazine, lomustine, and vincristine chemotherapy for anaplastic oligodendroglial tumors. Published online June 22, 2022. J Clin Oncol. 2022. doi:10.1200/JCO.21.02543}