P12.26.A PROGNOSIS IMPACT OF PROCARBAZINE AND/OR VINCRISTINE DISCONTINUATION IN FIRST-LINE TREATMENT BY PCV AND RADIOTHERAPY IN WHO GRADE 3 IDH-MUTANT DIFFUSE GLIOMAS

Abstract BACKGROUND WHO Grade 3 IDH-mutant diffuse gliomas (oligodendrogliomas (O3) or astrocytomas (A3)) are chemosensitive tumors. A POLA Network study recently showed a significant improvement in overall survival (OS) in patients with O3 treated by PCV (Procarbazine (PCZ), CCNU, Vincristine (VCR)) regimen in addition to radiotherapy (RT) versus Temozolomide and RT protocol. The same tendency was reported in A3 patients. However, the safety profile of PCV regimen is considered to be less favorable, leading to dose adaptation and early treatment discontinuation. The aim of our study was to describe the toxicity related to PCV regimen and the potential impact of an early PCZ or VCR discontinuation on progression-free survival (PFS) in patients with newly diagnosed O3 or A3. MATERIAL AND METHODS We analyzed the prospectively collected clinical, histo-molecular, survival and treatment data of patients with newly diagnosed A3 or O3 treated in first line by PCV and RT in 3 French POLA centers. All analyses were performed using RStudio (including “Maxstat” package). RESULTS A total of 191 patients were included (O3: 45.7% and A3: 54.3%) and 183 were analyzed for PFS after exclusion of early progression under treatment. Median follow-up was 65 months (range 14-145). Median PFS and median OS were not reached. 36.7% of patients received RT before PCV and median duration of PCV was 7 months (range 1-13). Grade 3/4 toxicities were reported in 78 patients (43%). The most common were cytopenia, occurring in 55 patients (30%), and liver cytolysis in 15 patients (8.2%). Dose reductions were required for PCZ and VCR in 10.9% and 52.5% of patients, respectively. Permanent treatment discontinuation occurred in 81 patients (44.2%) for PCZ and 97 patients (51.2%) for VCR. Neither the occurrence of grade 3/4 toxicity, nor PCV cycle delay (6 vs 8 weeks) impacted patient PFS. VCR dose decrease or premature discontinuation did not impact patient PFS. In contrast, a negative impact was observed in patients receiving less than 4 cycles of PCZ (p=0.037) or a total cumulative dose less than 4410 mg/m2 (p=0.049). CONCLUSION In newly patients diagnosed with a grade 3 IDH-mutant gliomas treated by RT and PCV, PCV toxicity, cycle delay or premature discontinuation of VCR did not impact patient PFS. However, PCZ discontinuation or reduced cumulative dose is associated to shorter PFS, highlighting the need for optimal PCZ toxicity management, including dose adaptation, cycle delay for toxicity recovery and improvement in symptom management.