INTELLANCE 2/EORTC 1410 randomized phase II study of Depatux-M alone and with temozolomide vs temozolomide or lomustine in recurrent EGFRamplified glioblastoma - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Neuro-Oncology Année : 2019

INTELLANCE 2/EORTC 1410 randomized phase II study of Depatux-M alone and with temozolomide vs temozolomide or lomustine in recurrent EGFRamplified glioblastoma

Martin van den Bent
Juan Manuel Sepulveda
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Marion Smits
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Annemiek Walenkamp
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Jean-Sebastian Frenel
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Paul Clement
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Filip de Vos
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Nicolas Whenham
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Paul Sanghera
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Michael Weller
H Dubbink
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Pim French
Jim Looman
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Jyotirmoy Dey
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Scott Krause
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Pete Ansell
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Sarah Nuyens
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Maarten Spruyt
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Joana Brilhante
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Thierry Gorlia
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Vassilis Golfinopoulos
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Résumé

Background: Depatuxizumab mafodotin (Depatux-M) is a tumor-specific antibody–drug conjugate consisting of an antibody (ABT-806) directed against activated epidermal growth factor receptor (EGFR) and the toxin monomethylauristatin-F. We investigated Depatux-M in combination with temozolomide or as a single agent in a randomized controlled phase II trial in recurrent EGFR amplified glioblastoma. Methods: Eligible were patients with centrally confirmed EGFR amplified glioblastoma at first recurrence after chemo-irradiation with temozolomide. Patients were randomized to either Depatux-M 1.25 mg/kg every 2 weeks intravenously, or this treatment combined with temozolomide 150–200 mg/m2 day 1–5 every 4 weeks, or either lomustine or temozolomide. The primary endpoint of the study was overall survival. Results: Two hundred sixty patients were randomized. In the primary efficacy analysis with 199 events (median follow-up 15.0 mo), the hazard ratio (HR) for the combination arm compared with the control arm was 0.71 (95% CI = 0.50, 1.02; P = 0.062). The efficacy of Depatux-M monotherapy was comparable to that of the control arm (HR = 1.04, 95% CI = 0.73, 1.48; P = 0.83). The most frequent toxicity in Depatux-M treated patients was a reversible corneal epitheliopathy, occurring as grades 3–4 adverse events in 25–30% of patients. In the long-term follow-up analysis with median follow-up of 28.7 months, the HR for the comparison of the combination arm versus the control arm was 0.66 (95% CI = 0.48, 0.93). Conclusion: This trial suggests a possible role for the use of Depatux-M in combination with temozolomide in EGFR amplified recurrent glioblastoma, especially in patients relapsing well after the end of first-line adjuvant temozolomide treatment. (NCT02343406)
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hal-02441092 , version 1 (03-07-2024)

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Martin van den Bent, Marica Eoli, Juan Manuel Sepulveda, Marion Smits, Annemiek Walenkamp, et al.. INTELLANCE 2/EORTC 1410 randomized phase II study of Depatux-M alone and with temozolomide vs temozolomide or lomustine in recurrent EGFRamplified glioblastoma. Neuro-Oncology, 2019, 22 (5), pp.684-693. ⟨10.1093/neuonc/noz222⟩. ⟨hal-02441092⟩
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