Radiotherapy Plus Procarbazine, Lomustine, and Vincristine Versus Radiotherapy Plus Temozolomide for IDH-Mutant Anaplastic Astrocytoma: A Retrospective Multicenter Analysis of the French POLA Cohort.
Anaplastic astrocytoma
IDH mutation
Procarbazine, lomustine, and vincristine
Temozolomide
Journal
The oncologist
ISSN: 1549-490X
Titre abrégé: Oncologist
Pays: England
ID NLM: 9607837
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
11
09
2020
accepted:
22
01
2021
pubmed:
2
2
2021
medline:
6
7
2021
entrez:
1
2
2021
Statut:
ppublish
Résumé
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. 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. 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). RT + PCV significantly improved PFS compared with RT + TMZ for IDH-mutant AA. However, RT + TMZ was better tolerated. 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.
Sections du résumé
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.
Identifiants
pubmed: 33524191
doi: 10.1002/onco.13701
pmc: PMC8100568
doi:
Substances chimiques
Procarbazine
35S93Y190K
Vincristine
5J49Q6B70F
Lomustine
7BRF0Z81KG
Temozolomide
YF1K15M17Y
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e838-e846Informations de copyright
© 2021 AlphaMed Press.
Références
Clin Neurol Neurosurg. 2016 Dec;151:31-36
pubmed: 27764705
J Neurooncol. 2016 Sep;129(3):505-514
pubmed: 27401154
Neuro Oncol. 2006 Jul;8(3):253-60
pubmed: 16723632
Neuro Oncol. 2019 Dec 17;21(12):1519-1528
pubmed: 31832685
Neuro Oncol. 2017 Feb 1;19(2):252-258
pubmed: 27994066
Histopathology. 2012 May;60(6):885-94
pubmed: 22335622
Neuro Oncol. 2016 Nov;18(11):1529-1537
pubmed: 27370396
J Clin Oncol. 2009 Dec 10;27(35):5881-6
pubmed: 19901104
J Clin Oncol. 2013 Jan 20;31(3):337-43
pubmed: 23071247
Lancet. 2017 Oct 7;390(10103):1645-1653
pubmed: 28801186
Asian Pac J Cancer Prev. 2015;16(2):411-20
pubmed: 25684464
Clin Neuroradiol. 2018 Sep;28(3):401-411
pubmed: 28466127
Can J Neurol Sci. 2010 Jan;37(1):36-42
pubmed: 20169771
Lancet Oncol. 2017 Jun;18(6):e315-e329
pubmed: 28483413
J Clin Oncol. 2014 Mar 10;32(8):783-90
pubmed: 24516018
J Clin Pathol. 2016 Aug;69(8):686-94
pubmed: 26743027
Acta Neuropathol. 2016 Jun;131(6):803-20
pubmed: 27157931
N Engl J Med. 2005 Mar 10;352(10):987-96
pubmed: 15758009
J Clin Oncol. 2013 Jan 20;31(3):344-50
pubmed: 23071237