Survival Outcomes Associated With First-Line Procarbazine, CCNU, and Vincristine or Temozolomide in Combination With Radiotherapy in IDH-Mutant 1p/19q-Codeleted Grade 3 Oligodendroglioma
Authors: Salah Eddine O. Kacimi, Caroline Dehais, Loïc Feuvret, Olivier Chinot, Catherine Carpentier, Charlotte Bronnimann, Elodie Vauleon, Apolline Djelad, Elizabeth Cohen-Jonathan Moyal, Olivier Langlois, Mario Campone, Mathilde Ducloie, Georges Noel, Stefania Cuzzubbo, Luc Taillandier, Carole Ramirez, Nadia Younan, Philippe Menei, Frédéric Dhermain, Christine Desenclos, François Ghiringhelli, Veronique Bourg, Damien Ricard, Thierry Faillot, Romain Appay, Emeline Tabouret, Lucia Nichelli, Bertrand Mathon, Alice Thomas, Suzanne Tran, Franck Bielle, Agusti Alentorn, J. Bryan Iorgulescu, Pierre-Yves Boëlle, Karim Labreche, Khê Hoang-Xuan, Marc Sanson, Ahmed Idbaih, Dominique Figarella-Branger, François Ducray, Mehdi Touat, C. Desenclos, N. Guillain, P. Menei, A. Rousseau, T. Cruel, S. Lopez, M. Abad, N. Hamdan, C. Adam, F. Parker, R. Seizeur, I. Quintin-Roué, G. Chotard, C. Bronnimann, D. Ricard, C. Godfraind, T. Khallil, D. Cazals-Hatem, T. Faillot, C. Gaultier, M.C. Tortel, I. Carpiuc, P. Richard, H. Aubriot-Lorton, F. Ghiringhelli, A. Djelad, C.A. Maurage, E.M. Gueye, F. Labrousse, F. Ducray, D. Meyronet, D. Figarella-Branger, O. Chinot, L. Bauchet, V. Rigau, G. Gauchotte, L. Taillandier, M. Campone, D. Loussouarn, V. Bourg, F. Vandenbos-Burel, J.-S. Guillamo, P. Roger, C. Blechet, H. Adle-Biassette, F. Bielle, A. Carpentier, C. Dehais, S. Milin, M. Wager, P. Colin, M.D. Diebold, D. Chiforeanu, E. Vauleon, F. Marguet, O. Langlois, F. Forest, M.J. Motso-Fotso, M. Andraud, B. Lhermitte, G. Noel, M. Bernier, N. Younan, C. Rousselot-Denis, I. Zemmoura, C. Joubert, E. Cohen-Moyal, E. Uro-Coste, F. Dhermain
Journal: Journal of Clinical Oncology (2024)

PURPOSE Patients with IDH-mutant 1p/19q-codeleted grade 3 oligodendroglioma (O3 IDHmt/Codel ) benefit from adding alkylating agent chemotherapy to radiotherapy (RT). However, the optimal chemotherapy regimen between procarbazine, 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), and vincristine (PCV) and temozolomide (TMZ) remains unclear given the lack of randomized trial data comparing both regimens. METHODS The objective was to assess the overall survival (OS) and progression-free survival (PFS) associated with first-line PCV/RT versus TMZ/RT in patients newly diagnosed with O3 IDHmt/Codel . We included patients with histologically proven O3 IDHmt/Codel (according to WHO criteria) from the French national prospective cohort Prise en charge des OLigodendrogliomes Anaplasiques (POLA). All tumors underwent central pathological review. OS and PFS from surgery were estimated using the Kaplan-Meier method and Cox regression model. RESULTS 305 newly diagnosed patients with O3 IDHmt/Codel treated with RT and chemotherapy between 2008 and 2022 were included, of which 67.9% of patients (n = 207) were treated with PCV/RT and 32.1% with TMZ/RT (n = 98). The median follow-up was 78.4 months (IQR, 44.3-102.7). The median OS was not reached (95% CI, Not reached [NR] to NR) in the PCV/RT group and was 140 months (95% CI, 110 to NR) in the TMZ/RT group (log-rank P = .0033). On univariable analysis, there was a significant difference in favor of PCV/RT in both 5-year (PCV/RT: 89%, 95% CI, 85 to 94; TMZ/RT: 75%, 95% CI, 66 to 84) and 10-year OS (PCV/RT: 72%, 95% CI, 61 to 85; TMZ/RT: 60%, 95% CI, 49 to 73), which was confirmed using the multivariable Cox model adjusted for age, type of surgery, gender, Eastern Cooperative Oncology Group performance status, and CDKN2A homozygous deletion (hazard ratio, 0.53 for PCV/RT, 95% CI, 0.30 to 0.92, P = .025). CONCLUSION In patients with newly diagnosed O3 IDHmt/Codel from the POLA cohort, first-line PCV/RT was associated with better OS outcomes compared with TMZ/RT. Our data suggest that the improved safety profile associated with TMZ comes at the cost of inferior efficacy in this population. Further investigation using prospective randomized studies is warranted.