Journal article
INTELLANCE 2/EORTC 1410 randomized phase II study of Depatux-M alone and with temozolomide vs temozolomide or lomustine in recurrent EGFR amplified glioblastoma.
- Van Den Bent M Brain Tumor Institute Erasmus Medical Center (MC) Cancer Institute, Rotterdam, the Netherlands.
- Eoli M Department of Neurology, Carlo Besta Institute, Milan, Italy.
- Sepulveda JM University Hospital 12 October, Madrid, Spain.
- Smits M Department of Radiology, Erasmus MC, Rotterdam, the Netherlands.
- Walenkamp A Department of Medical Oncology, University Medical Center Groningen, Groningen, the Netherlands.
- Frenel JS Department of Medical Oncology, René Gauducheau Center for Cancer Care, Nantes, France.
- Franceschi E Department of Medical Oncology, Local Health Unit Agency/Scientific Institute for Research, Hospitalization, and Healthcare (AUSL/IRCCS) Neurological Sciences, Bologna, Italy.
- Clement PM Department of Medical Oncology, Leuven Cancer Institute, KU Leuven, Leuven, Belgium.
- Chinot O Department of Neuro-Oncology, Institute of Neurophysiopathology, Aix-Marseille University, Marseille, France.
- De Vos F Department of Medical Oncology, University Medical Center Utrecht, Utrecht, the Netherlands.
- Whenham N Department of Medical Oncology, European Organisation for Research and Treatment of Cancer (EORTC), Brussels, Belgium.
- Sanghera P University Hospitals Birmingham, Birmingham, UK.
- Weller M Department of Neurology, University Hospital Zurich, Zurich, Switzerland.
- Dubbink HJ Department of Pathology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
- French P Brain Tumor Institute Erasmus Medical Center (MC) Cancer Institute, Rotterdam, the Netherlands.
- Looman J Abbvie, Chicago, IL USA.
- Dey J Department of Neurology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
- Krause S Abbvie, Chicago, IL USA.
- Ansell P Abbvie, Chicago, IL USA.
- Nuyens S EORTC Headquarters, Brussels, Belgium.
- Spruyt M Brain Tumor Institute Erasmus Medical Center (MC) Cancer Institute, Rotterdam, the Netherlands.
- Brilhante J EORTC Headquarters, Brussels, Belgium.
- Coens C EORTC Headquarters, Brussels, Belgium.
- Gorlia T EORTC Headquarters, Brussels, Belgium.
- Golfinopoulos V EORTC Headquarters, Brussels, Belgium.
- 2019-11-21
Published in:
- Neuro-oncology. - 2020
English
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).
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).
- Language
-
- English
- Open access status
- hybrid
- Identifiers
-
- DOI 10.1093/neuonc/noz222
- PMID 31747009
- Persistent URL
- https://folia.unifr.ch/global/documents/153118
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