Radiotherapy-PCV versus radiotherapy-temozolomide for IDH-mutant anaplastic astrocytoma: a retrospective multicentre analysis of the French POLA cohort.

Abstract

BACKGROUND\nIDH-mutant anaplastic astrocytomas (AA) are chemosensitive tumours for which the best choice of adjuvant chemotherapy between procarbazine, CCNU and vincristine (PCV) or temozolomide (TMZ) after radiotherapy (RT) remains unclear.\n\n\nMETHODS\nIn a large cohort of patients with histologically proven WHO 2016 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.\n\n\nRESULTS\nThe 4-year PFS in the RT + PCV arm was 70.8% vs 53.5% in the RT + TMZ arm, with a hazard ratio (HR) of 0.58 CI95% [0.38; 0.87], P=0.0074 in univariable analysis and 0.63 CI95% [0.41; 0.97], P=0.0348 in multivariable analysis. The 4-year OS in the RT + PCV arm was 84.3% vs 76.6% in the RT + TMZ arm, with a HR of 0.57 CI95% [0.30; 1.05], P=0.0675 in univariable analysis. Toxicity was significantly higher in the RT + PCV arm with more grade ≥3 toxicity (46.7% versus 8.6%, P<0.0001).\n\n\nCONCLUSIONS\nRT + PCV significantly improved PFS compared to RT + TMZ for IDH-mutant AA. However, RT + TMZ was better tolerated.\n\n\nIMPLICATIONS FOR PRACTICE\nIn the absence of fully conducted randomized trials comparing PCV to TMZ in adjuvant treatment after RT for the management of IDH-mutant AA and a similar level of evidence, these two chemotherapies are both equally recommended in international guidelines. Our study in a national cohort of IDH-mutant AA defined according the 2016 WHO classification shows for the first time that the RT + PCV regimen significantly improves PFS in comparison to the RT + TMZ regimen. Even if at the time of analysis the difference in OS 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.