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Radiotherapy Plus Procarbazine,Lomustine, and Vincristine Versus Radiotherapy Plus Temozolomide for IDH-Mutant Anaplastic Astrocytoma: A Retrospective Multicenter Analysis of the French POLA Cohort |
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| Authors: | Vincent Esteyrie Caroline Dehais Elodie Martin Catherine Carpentier Emmanuelle Uro-Coste Dominique Figarella-Branger Charlotte Bronniman Damien Pouessel Delphine Larrieu Ciron François Ducray Elizabeth Cohen-Jonathan Moyal Pola Network |
| Affiliation: | 1. Department of Radiotherapy, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse, Oncopole 1, Toulouse, France;2. Department of Neurology 2-Mazarin, Public Assistance–Paris Hospitals (APHP), University Hospital Pitié Salpêtrière-Charles Foix, Paris, France;3. Department of Biostatistics, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse, Oncopole 1, Toulouse, France;4. Department of Neurology 2-Mazarin, Public Assistance–Paris Hospitals (APHP), University Hospital Pitié Salpêtrière-Charles Foix, Paris, France Brain and Spinal Cord Institute, Sorbonne University and University Hospital Pitié Salpêtrière-Charles Foix, National Institute of Health and Medical Research (INSERM), Centre National de la Recherche Scientifique (CNRS), Paris, France;5. Department of Pathology and Histology-Cytology, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse, Oncopole 1, Toulouse, France;6. Department of Pathology and Neuropathology, Timone Hospital, Public Assistance–Marseille Hospitals (APHM), Marseille, France;7. Department of Oncology, Saint-André Hospital, Centre Hospitalier Universitaire de Bordeaux 1, Bordeaux, France;8. Department of Oncology, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse, Oncopole 1, Toulouse, France;9. Department of Neuro-Oncology, Civil Hospices of Lyon, Pierre Wertheimer Hospital, Lyon, France;10. Department of Radiotherapy, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse, Oncopole 1, Toulouse, France Université Paul Sabatier, Toulouse III, Toulouse, France |
| Abstract: | Background IDH‐mutant anaplastic astrocytomas (AAs) are chemosensitive tumors for which the best choice of adjuvant chemotherapy between procarbazine, lomustine, and vincristine (PCV) or temozolomide (TMZ) after radiotherapy (RT) remains unclear.MethodsIn a large cohort of patients with histologically proven 2016 World Health Organization classification AA with IDH1/2 mutations included in the French national POLA cohort (n = 355), the primary objective was to compare progression‐free survival (PFS) between the two treatment regimens (n = 311). Secondary endpoints were overall survival (OS), progression type, pseudoprogression rate, and toxicity.ResultsThe 4‐year PFS in the RT + PCV arm was 70.8% versus 53.5% in the RT + TMZ arm, with a hazard ratio (HR) of 0.58 (95% confidence interval [CI], 0.38–0.87; p = .0074) in univariable analysis and 0.63 (95% CI, 0.41–0.97; p = .0348) in multivariable analysis. The 4‐year OS in the RT + PCV arm was 84.3% versus 76.6% in the RT + TMZ arm, with an HR of 0.57 (95% CI, 0.30–1.05; p = .0675) in univariable analysis. Toxicity was significantly higher in the RT + PCV arm with more grade ≥3 toxicity (46.7% vs. 8.6%, p < .0001).ConclusionRT + PCV significantly improved PFS compared with RT + TMZ for IDH‐mutant AA. However, RT + TMZ was better tolerated.Implications for PracticeIn the absence of fully conducted randomized trials comparing procarbazine, lomustine, and vincristine (PCV) with temozolomide (TMZ) in adjuvant treatment after radiotherapy (RT) for the management of IDH‐mutant anaplastic astrocytoma (AA) and a similar level of evidence, these two chemotherapies are both equally recommended in international guidelines. This study in a national cohort of IDH‐mutant AA defined according the 2016 World Health Organization (WHO) classification shows for the first time that the RT + PCV regimen significantly improves progression‐free survival in comparison with the RT + TMZ regimen. Even if at the time of analysis the difference in overall survival was not significant, this result provides new evidence for the debate about the chemotherapy regimen to prescribe in adjuvant treatment to RT for WHO 2016 IDH‐mutant AA. |
| Keywords: | Anaplastic astrocytoma Temozolomide Procarbazine, lomustine, and vincristine IDH mutation |