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
Abstract
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.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (110)
Salah Eddine O. Kacimi
Institut du Cerveau, Paris Brain Institute (ICM), Inserm, CNRS, Sorbonne Université, AP-HP, SIRIC CURAMUS, Paris, France
Caroline Dehais
Service de Neuro-oncologie, Sorbonne Université, Inserm, CNRS, UMR S 1127, Institut du Cerveau, Paris Brain Institute, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière—Charles Foix, Paris, France
Loic Feuvret
Olivier Chinot
Hôpital La Timone, Marseille, France
Catherine Carpentier
Institut du Cerveau, Paris Brain Institute (ICM), Inserm, CNRS, Sorbonne Université, AP-HP, SIRIC CURAMUS, Paris, France
Charlotte Bronnimann
University Hospital of Bordeaux, Department of Medical Oncology, Bordeaux, France
Elodie Vauleon
Department of Medical Oncology and Radiotherapy, Centre Eugène Marquis, Rennes, France
Apolline Djelad
Department of Neurosurgery, University Hospital of Lille, Lille, France
Elizabeth Cohen-Jonathan Moyal
Université de Toulouse, Oncopole Claudius Regaud, IUCT-Oncopole, Toulouse, France
Olivier Langlois
Department of Neurosurgery, University Hospital of Rouen, Rouen, France
Mario Campone
Institut de Cancérologie de l’Ouest Angers-Nantes, Saint-Herblain, France
Mathilde Ducloie
CHU Côte de Nacre, Neurosurgery Department, Caen, France
Georges Noël
Stefania Cuzzubbo
Luc Taillandier
19CHU Nancy, Neuro-Oncology, Nancy, France
Carole Ramirez
Neurology Department, North Hospital, University Hospital of Saint Etienne, Saint-Priest-en-Jarez, France
Nadia Younan
Neurology Department, Hôpital Foch, Suresnes, France
Philippe Menei
Neurosurgery Department, CHU Angers, Angers, France
Frédéric Dhermain
Christine Desenclos
Neurosurgery Department, Hôpital Nord, CHU Amiens, Amiens, France
François Ghiringhelli
Veronique Bourg
Neurology Department, CHU Nice, Nice, France
Damien Ricard
Neurology department, Hôpital National d'Instruction des Armées Percy, Service de Santé des Armées, Clamart, France
Thierry Faillot
Neurosurgery Department, AP-HP, Hôpital Beaujon, Clichy, France
Romain Appay
Department of Pathology and Neuropathology, Aix-Marseille University, CHU Timone, AP-HM, Marseille, France
Emeline Tabouret
Department of Neuro-Oncology, Aix-Marseille Université, CHU Timone, AP-HM, Marseille, France
Lucia Nichelli
1Hôpital Pitié-Salpêtrière, Paris, France
Bertrand Mathon
Alice Thomas
Service de Radiothérapie, Hôpitaux Universitaires La Pitié Salpêtrière—Charles Foix, AP-HP, Sorbonne Université, Paris, France
Suzanne Tran
Institut du Cerveau, Paris Brain Institute (ICM), Inserm, CNRS, Sorbonne Université, AP-HP, SIRIC CURAMUS, Paris, France
Franck Bielle
Agusti Alentorn
Institut du Cerveau, Paris Brain Institute (ICM), Inserm, CNRS, Sorbonne Université, AP-HP, SIRIC CURAMUS, Paris, France
J. Bryan Iorgulescu
Pierre-Yves Boëlle
Sorbonne Université, CinBioS, UMS 37 PASS, INSERM, Paris, France
Karim Labreche
Institut du Cerveau, Paris Brain Institute (ICM), Inserm, CNRS, Sorbonne Université, AP-HP, SIRIC CURAMUS, Paris, France
Khe Hoang-Xuan
1Hôpital Pitié-Salpêtrière, Paris, France
Marc Sanson
Ahmed Idbaih
3Pitie Salpetriere Hospital, Paris, France
Dominique Figarella-Branger
Department of Pathology and Neuropathology, Aix-Marseille University, CHU Timone, AP-HM, Marseille, France
François Ducray
Neuro-Oncology Department, Hospices Civils de Lyon, Cancer Research Center of Lyon, Université Lyon 1, Lyon, France
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