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

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; POLA Network

doi:10.1200/JCO.24.00049

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

J Clin Oncol. 2024 Oct 2:JCO2400049. doi: 10.1200/JCO.24.00049. Online ahead of print.

Authors

Salah Eddine O Kacimi^{1

2}, Caroline Dehais^{1

3}, Loïc Feuvret⁴, Olivier Chinot⁵, Catherine Carpentier¹, Charlotte Bronnimann⁶, Elodie Vauleon⁷, Apolline Djelad⁸, Elizabeth Cohen-Jonathan Moyal^{9

10

11}, Olivier Langlois¹², Mario Campone¹³, Mathilde Ducloie¹⁴, Georges Noel^{15

16}, Stefania Cuzzubbo^{17

18}, Luc Taillandier¹⁹, Carole Ramirez²⁰, Nadia Younan²¹, Philippe Menei²², Frédéric Dhermain²³, Christine Desenclos²⁴, François Ghiringhelli²⁵, Veronique Bourg²⁶, Damien Ricard²⁷, Thierry Faillot²⁸, Romain Appay²⁹, Emeline Tabouret⁵, Lucia Nichelli^{1

30}, Bertrand Mathon^{1

31}, Alice Thomas³², Suzanne Tran^{1

33}, Franck Bielle^{1

33}, Agusti Alentorn^{1

3}, J Bryan Iorgulescu³⁴, Pierre-Yves Boëlle², Karim Labreche^{1

2}, Khê Hoang-Xuan^{1

3}, Marc Sanson^{1

3}, Ahmed Idbaih^{1

3}, Dominique Figarella-Branger²⁹, François Ducray^{35

36}, Mehdi Touat^{1

3

37}; POLA Network

Collaborators

POLA Network:
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

Affiliations

¹ Institut du Cerveau, Paris Brain Institute (ICM), Inserm, CNRS, Sorbonne Université, AP-HP, SIRIC CURAMUS, Paris, France.
² Sorbonne Université, CinBioS, UMS 37 PASS, INSERM, Paris, France.
³ Service de Neuro-oncologie, Hôpitaux Universitaires La Pitié Salpêtrière-Charles Foix, AP-HP, Sorbonne Université, Paris, France.
⁴ Hospices Civils de Lyon, Radiotherapy Department, Bron, France.
⁵ Department of Neuro-Oncology, Aix-Marseille Université, CHU Timone, AP-HM, Marseille, France.
⁶ Department of Medical Oncology, University Hospital of Bordeaux, Bordeaux, France.
⁷ Centre Eugène Marquis, Medical Oncology, INSERM U1242, University of Rennes, Rennes, France.
⁸ Department of Neurosurgery, University Hospital of Lille, Lille, France.
⁹ Department of Radiation Oncology, Claudius Regaud/Institut Universitaire du Cancer de Toulouse - Oncopole, Toulouse, France.
¹⁰ Institut National de la Santé et de la Recherche Médicale U1037, Centre de Recherche contre le Cancer de Toulouse, Toulouse, France.
¹¹ Université Toulouse III Paul Sabatier, Toulouse, France.
¹² Department of Neurosurgery, University Hospital of Rouen, Rouen, France.
¹³ Institut de Cancérologie de l'Ouest-René Gauducheau, Centre de Recherche en Cancérologie, Saint Herblain, France.
¹⁴ Department of Neurology, CHU de Caen Normandie, Caen, France.
¹⁵ Radiation Oncology Department, Institut de cancérologie Strasbourg Europe (ICANS), Strasbourg, France.
¹⁶ Radiobiology Laboratory, Centre Paul Strauss, IIMIS - Imagerie Multimodale Integrative en Santé, ICube, Strasbourg University, Strasbourg, France.
¹⁷ Neurology Department, APHP, University Hospital Saint Louis, Paris, France.
¹⁸ Université Paris Cité, Paris, France.
¹⁹ Neurology Department, CHU de Nancy, Nancy, France.
²⁰ Neurology Department, North Hospital, University Hospital of Saint Etienne, Saint-Priest-en-Jarez, France.
²¹ Neurology Department, Hôpital Foch, Suresnes, France.
²² Neurosurgery Department, CHU Angers, Angers, France.
²³ Radiotherapy Department, Institut Gustave Roussy, Villejuif, France.
²⁴ Neurosurgery Department, Hôpital Nord, CHU Amiens, Amiens, France.
²⁵ Centre Georges-François Leclerc, Medical Oncology, Dijon, France.
²⁶ Neurology Department, CHU Nice, Nice, France.
²⁷ Neurology department, Hôpital National d'Instruction des Armées Percy, Service de Santé des Armées, Clamart, France.
²⁸ Neurosurgery Department, AP-HP, Hôpital Beaujon, Clichy, France.
²⁹ Department of Pathology and Neuropathology, Aix-Marseille University, CHU Timone, AP-HM, Marseille, France.
³⁰ Service de Neuroradiologie, Hôpitaux Universitaires La Pitié Salpêtrière-Charles Foix, AP-HP, Sorbonne Université, Paris, France.
³¹ Service de Neurochirurgie, Hôpitaux Universitaires La Pitié Salpêtrière-Charles Foix, AP-HP, Sorbonne Université, Paris, France.
³² Service de Radiothérapie, Hôpitaux Universitaires La Pitié Salpêtrière-Charles Foix, AP-HP, Sorbonne Université, Paris, France.
³³ Service de Neuropathologie, Hôpitaux Universitaires La Pitié Salpêtrière-Charles Foix, AP-HP, Sorbonne Université, Paris, France.
³⁴ Molecular Diagnostics Laboratory, Division of Pathology and Laboratory Medicine, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX.
³⁵ Neuro-Oncology Unit, Hospices Civils de Lyon, Lyon, France.
³⁶ LabEx Dev2CAN, Institut Convergence Plascan, Centre de Recherche en Cancérologie de Lyon, Inserm U1052, CNRS UMR5286, Université de Lyon, Université Claude Bernard, Villeurbanne, France.
³⁷ Department of Neurology, Brigham and Women's Hospital, Boston, MA.

PMID: 39356975
DOI: 10.1200/JCO.24.00049

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 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.