放疗联合丙卡巴肼、洛莫司汀和长春新碱与放疗联合替莫唑胺治疗异柠檬酸脱氢酶（IDH）突变型间变性星形细胞瘤的疗效比较：法国POLA队列的回顾性多中心分析
Radiotherapy Plus Procarbazine, Lomustine, and Vincristine Versus Radiotherapy Plus Temozolomide for IDH-Mutant Anaplastic Astrocytoma: A Retrospective Multicenter Analysis of the French POLA Cohort.
作者信息
Esteyrie Vincent, Dehais Caroline, Martin Elodie, Carpentier Catherine, Uro-Coste Emmanuelle, Figarella-Branger Dominique, Bronniman Charlotte, Pouessel Damien, Ciron Delphine Larrieu, Ducray François, Moyal Elizabeth Cohen-Jonathan, Network Pola
机构信息
Department of Radiotherapy, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse, Oncopole 1, Toulouse, France.
Department of Neurology 2-Mazarin, Public Assistance-Paris Hospitals (APHP), University Hospital Pitié Salpêtrière-Charles Foix, Paris, France.
出版信息
Oncologist. 2021 May;26(5):e838-e846. doi: 10.1002/onco.13701. Epub 2021 Feb 15.
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.
METHODS
In 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.
RESULTS
The 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).
CONCLUSION
RT + PCV significantly improved PFS compared with RT + TMZ for IDH-mutant AA. However, RT + TMZ was better tolerated.
IMPLICATIONS FOR PRACTICE
In 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.
背景
异柠檬酸脱氢酶（IDH）突变的间变性星形细胞瘤（AA）是对化疗敏感的肿瘤，放疗（RT）后辅助化疗选择丙卡巴肼、洛莫司汀和长春新碱（PCV）或替莫唑胺（TMZ）哪种最佳仍不明确。
方法
在法国全国性POLA队列中纳入的一大群经组织学证实为2016年世界卫生组织分类的伴有IDH1/2突变的AA患者（n = 355）中，主要目的是比较两种治疗方案（n = 311）的无进展生存期（PFS）。次要终点包括总生存期（OS）、进展类型、假性进展率和毒性。
结果
RT + PCV组的4年PFS为70.8%，而RT + TMZ组为53.5%，单变量分析中的风险比（HR）为0.58（95%置信区间[CI]，0.38 - 0.87；p = 0.0074），多变量分析中的HR为0.63（95%CI，0.41 - 0.97；p = 0.0348）。RT + PCV组的4年OS为84.3%，而RT + TMZ组为76.6%，单变量分析中的HR为0.57（95%CI，0.30 - 1.05；p = 0.0675）。RT + PCV组的毒性显著更高，≥3级毒性更多（46.7%对8.6%，p < 0.0001）。
结论
对于IDH突变的AA，与RT + TMZ相比，RT + PCV显著改善了PFS。然而，RT + TMZ的耐受性更好。
实践意义
在缺乏将丙卡巴肼、洛莫司汀和长春新碱（PCV）与替莫唑胺（TMZ）用于放疗（RT）后辅助治疗IDH突变的间变性星形细胞瘤（AA）进行全面比较的随机试验以及类似证据水平的情况下，国际指南中同样推荐这两种化疗方法。这项针对根据2016年世界卫生组织（WHO）分类定义的IDH突变AA全国队列的研究首次表明，与RT + TMZ方案相比，RT + PCV方案显著改善了无进展生存期。即使在分析时总生存期差异不显著，这一结果也为关于WHO 2016 IDH突变AA放疗后辅助治疗中化疗方案选择的争论提供了新证据。
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