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