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Article Dans Une Revue Journal of Clinical Oncology Année : 2021

Olaparib in recurrent IDH-mutant high-grade glioma (OLAGLI).

Francois Ducray
  • Fonction : Auteur
Marc Sanson
Maxime Fontanilles
  • Fonction : Auteur
Romain Rivoirard
Laure Thomas-Maisonneuve
  • Fonction : Auteur
Stephanie Cartalat
  • Fonction : Auteur
Alice Bonneville-Levard
  • Fonction : Auteur
Amelie Darlix
Roxana Ameli
  • Fonction : Auteur
David Meyronet
Francois Gueyffier
  • Fonction : Auteur
Laurent Remontet
  • Fonction : Auteur
Delphine Maucort-Boulch
Caroline Dehais
  • Fonction : Auteur
Jerôme Honnorat
  • Fonction : Auteur

Résumé

2007 Background: There is a need to develop new treatments in IDH-mutant high-grade gliomas recurring after radiotherapy and chemotherapy. Based on preclinical studies showing that IDH-mutant tumors could be vulnerable to PARP inhibition we launched a phase II study to test the efficacy of olaparib (Lynparza) monotherapy in this population. Methods: Adults with recurrent high-grade IDH-mutant gliomas after radiotherapy and at least one line of alkylating chemotherapy (PCV or TMZ), KPS > 60, normal organ function were enrolled. The primary endpoint was 6 months PFS according to RANO criteria. Patients were treated with olaparib 300 mg twice daily. We used a single-stage Fleming design with p0 = 30%, p1 = 50%, a type I unilateral error rate of 5% and a power of 80%. Results: 35 patients with recurrent IDH-mutant gliomas (IDH1R132H-mutant n = 32, other IDH mutation n = 3, 1p/19 codeleted n = 16, 1p/19q non-codeleted n = 14) were enrolled (malignantly transformed low-grade gliomas n = 21, anaplastic gliomas n = 8, glioblastomas n = 6). Median time since diagnosis was 7.4 years (1-22 years), median time since radiotherapy was 2.8 years (0.6-18 years), median number of previous chemotherapy lines was 2 (1-5). With a median follow-up of 11 months, 30 patients had stopped treatment due to tumor progression and 2 patients were still on treatment 16 to 18 months after treatment start. At 6 months, 11/35 patients were progression-free (31 %). According to RANO criteria, based on local investigator analysis, 2 patients (5%) had a partial response and 14 patients a stable disease (37%) with a median duration of response of 9 months (4-18 months+). Median PFS and OS were 2.3 and 15.9 months and were similar in 1p/19q codeleted and non-codeleted patients. A grade 3 olaparib-related adverse event was observed in 5 patients (14%, lymphopenia n = 3, fatigue n = 2, diarrhea n = 1) and a grade 2 in 15 patients (43%), most frequently consisting in fatigue (23%), gastrointestinal disorders (20%) and lymphopenia (20%). No patient definitively stopped olaparib due to side effects. Conclusions: In this heavily pre-treated population of recurrent IDH-mutant gliomas, olaparib monotherapy was well tolerated and resulted in some activity supporting its evaluation in association with alkylating chemotherapy in recurrent IDH-mutant gliomas in future studies. Clinical trial information: NCT03561870.
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Dates et versions

hal-03603885 , version 1 (10-03-2022)

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Citer

Francois Ducray, Marc Sanson, Olivier Chinot, Maxime Fontanilles, Romain Rivoirard, et al.. Olaparib in recurrent IDH-mutant high-grade glioma (OLAGLI).. Journal of Clinical Oncology, 2021, 39 (15_suppl), pp.2007-2007. ⟨10.1200/JCO.2021.39.15_suppl.2007⟩. ⟨hal-03603885⟩
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