According to long-term data, first-line treatment with procarbazine, lomustine, and vincristine chemotherapy plus radiotherapy offered prolonged disease control and survival benefit in anaplastic oligodendroglial tumors.
Long-term follow-up findings from the phase 3 EORTC 26951 (NCT00002840) and RTOG 9402 (NCT00002569) trials assessing procarbazine (Matulane), lomustine (Gleostine), and vincristine (PCV) chemotherapy plus radiotherapy prolonged disease control and survival in the first line compared with radiotherapy alone in patients with anaplastic oligodendroglial tumors.
In EORTC 26951, the median follow-up for progression-free survival (PFS) and overall survival (OS) was 19 years; median follow-up for surviving patients who were progression free was 17.7 years and median for surviving patients overall was 17.8 years. PFS (HR, 0.69; 95% CI, 0.55-0.86; P = .001) and OS (HR, 0.78; 95% CI, 0.63-0.98; P = .033) outcomes were better with PCV and radiotherapy vs radiotherapy alone. Moreover, in the RTOG 9402 trial, the median follow-up was 17.4 years for patients who were still alive and progression free and 18.1 years for surviving patients. The combination resulted in a statistically significant improvement in PFS vs radiotherapy (HR, 0.67; 95% CI, 0.52-0.86), although the same was not observed for OS (HR, 0.79; 95% CI, 0.61-1.03).
“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 PCV chemotherapy to RT lengthens disease control and survival relative to RT alone as first-line therapy for anaplastic oligodendroglial tumors, particularly among 1p/19q codeleted cases,” the study’s investigators wrote.
In both studies, radiotherapy was administered at a total dose of 59.4 Gy in 33 fractions of 1.8 Gy each. Patients who enrolled on the EORTC 26951 study were treated with 6 cycles of adjuvant PCV following radiotherapy. Moreover, those who were included in the RTOG 9402 study received 4 cycles of treatment with intensified PCV following radiotherapy.
A total of 368 patients were included in the EORTC 26951 study. Twenty-five percent of patients had codeletion of 1p/19q by fluorescent in situ hybridization and 46% had an IDH1/2 mutation detected via Sanger sequencing. Among 80 patients with 1p/19q codeleted tumors, 26 were alive at last follow-up. For this population, the HR for PFS was 0.49 (95% CI, 0.29-0.83; P = .007) and 0.60 for OS (95% CI, 0.35-1.03; P = .063). The HRs for PFS and OS among patients with mutant IDH and no 1p/19q codeletion (n = 43) were 0.57 (95% CI, 0.29-1.10; P = .091) and 0.60 (95% CI, 0.31-1.17; P = .131).
Additionally, 289 patients were randomized in the RTOG 9402 study. Of these patients, 21% were still alive and 16% were free of progression as of May 2018. In this population, 48% had FISH codeletion and 74% had IDH mutations. Almost all IDH-mutant tumors also had 1p/19q codeletion (90%). In the population of patients with 1p/19q codeleted tumors (n = 125), treatment with PCV was associated with longer PFS (HR, 0.61; 95% CI, 0.40-0.94; P = .02) and OS (HR, 0.46; 95% CI, 0.30-0.70; P <.001) vs radiotherapy alone. In the population of patients with non-codeleted IDH-mutant tumors (n = 66), PFS was significantly longer following treatment with PCV and radiotherapy compared with radiotherapy alone (HR, 0.58; P = .046) with a trend towards prolonged OS (HR, 0.60; P = .06).
Lassman AB, Hoang-Xuan K, Polley MYC, et al. Joint final report of EORTC 26951 and RTOG 9402: phase III trials with procarbazine, lomustine, and vincristine chemotherapy for anaplastic oligodendroglial tumors. J Clin Oncol. Published online 22, 2022. doi:10.1200/JCO.21.02543