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First-Line Radiotherapy With or Without Procarbazine, Lomustine, and Vincristine Chemotherapy for Anaplastic Oligodendroglial Tumors


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As reported in the Journal of Clinical Oncology by Lassman et al, final survival reports from long-term follow-up of the phase III EORTC 26951 and RTOG 9402 studies show continued benefit of the addition of (neo)adjuvant procarbazine, lomustine, and vincristine to radiotherapy in patients with newly diagnosed anaplastic oligodendroglial tumors, particularly among patients with 1p19q codeletion.

Study Details 

In EORTC 26951, 368 patients were randomly assigned between August 1996 and March 2002 to receive up to six cycles of adjuvant procarbazine, lomustine, and vincristine after radiotherapy (n = 185) or radiotherapy alone (n = 183). In RTOG 9402, 289 patients were randomly assigned between July 1994 and March 2002 to receive up to four cycles of intensified procarbazine, lomustine, and vincristine before radiotherapy (n = 146) or radiotherapy alone (n = 143). In both studies, radiotherapy was administered to a total dose of 59.4 Gy in 33 fractions of 1.8 Gy.

Both trials showed that the addition of procarbazine, lomustine, and vincristine chemotherapy to radiotherapy lengthens disease control and survival relative to radiotherapy alone as first-line therapy for anaplastic oligodendroglial tumors, particularly among 1p/19q codeleted cases.
— Lassman et al

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Key Findings

Median follow-up in both studies was between 18 and 19 years.

In EORTC 26951, for the procarbazine, lomustine, and vincristine-plus-radiotherapy group vs radiotherapy-alone group, median overall survival was 3.5 years vs 2.6 years; 14-year survival was 25.1% vs 13.4%; and probable 20-year survival was 16.8% vs 10.1% (hazard ratio [HR] = 0.78, 95% confidence interval [CI] = 0.63­–0.98, P = .033). Among 43 vs 37 patients with 1p19q codeletion, median overall survival was 14.2 years vs 9.3 years; 14-year survival was 51.0% vs 26.2%; and probable 20-year survival was 37.1% vs 13.6% (HR = 0.60, 95% CI = 0.35–1.03, P = .063). In the total population, progression-free survival rates at 10 and 14 years were 26.1% vs 13.3% and 22.7% vs 10.4% (HR = 0.69, 95% CI = 0.55–0.86).

In RTOG 9402, for the procarbazine, lomustine, and vincristine plus radiotherapy group vs radiotherapy alone group, median overall survival was 4.8 years vs 4.8 years; 14-year survival was 29.1% vs 16.5%; and probable 20-year survival was 24.6% vs 11.2% (HR = 0.79, 95% CI = 0.61–1.03, P = .08). Among 58 vs 67 patients with 1p19q codeletion, median overall survival was 13.2 years vs 7.3 years; 14-year survival was 46.1% vs 25.0%; and probable 20-year survival was 37% vs 14.9% (HR = 0.61, 95% CI = 0.40–0.94, P = .02). In the total population, progression-free survival rates at 10 and 14 years were 30.8% vs 11.1% and 25.7% vs 9.6% (HR = 0.67, 95% CI = 0.52-0.86).

The investigators concluded, “With that, the studies show similar long-term survival even without tumor recurrence in a significant proportion of patients after first-line treatment with radiotherapy/procarbazine, lomustine, and vincristine.”

They noted, “EORTC 26951 and RTOG 9402 were practice-changing phase III trials. Here, we report very long-term mature and final survival analyses nearly 30 years after the trials were conceived. Both trials showed that the addition of procarbazine, lomustine, and vincristine chemotherapy to radiotherapy lengthens disease control and survival relative to radiotherapy alone as first-line therapy for anaplastic oligodendroglial tumors, particularly among 1p/19q codeleted cases.”

Martin J. van den Bent, MD, of the Brain Tumor Center, Erasmus MC Cancer Institute, Erasmus University Hospital, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The work was supported by the National Cancer Institute, EORTC Research Fund, and others. For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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