Impact of depatuxizumab mafodotin on health-related quality of life and neurological functioning in the phase II EORTC 1410/INTELLANCE 2 trial for EGFR-amplified recurrent glioblastoma.

BACKGROUND

In the EORTC 1410/INTELLANCE 2 randomised, phase II study (NCT02343406), with the antibody-drug conjugate depatuxizumab mafodotin (Depatux-M, ABT-414) in patients with recurrent EGFR-amplified glioblastoma, the primary end-point (overall survival) was not met, and the drug had ocular dose-limiting toxicity. This study reports results from the prespecified health-related quality of life (HRQoL) and neurological deterioration-free survival (NDFS) exploratory analysis.

PATIENTS AND METHODS

Patients (n = 260) were randomised 1:1:1 to receive either Depatux-M 1.25 mg/kg or 1.0 mg/kg intravenously every 2 weeks with oral temozolomide (TMZ) 150 mg/m

RESULTS

Compliance with HRQoL was 88.1% at baseline and decreased to 37.9% at month 6. Differences from baseline between Depatux-M arms and TMZ/CCNU in global health/QoL status throughout treatment did not reach clinical relevance (≥10 points). Self-reported visual disorders deteriorated to a clinically relevant extent with Depatux-M arms versus TMZ/CCNU at all timepoints (mean differences range: 24.6-35.1 points). Changes from baseline for other HRQoL scales and NDFS were generally similar between treatment arms.

CONCLUSIONS

Depatux-M had no impact on HRQoL and NDFS in patients with EGFR-amplified recurrent glioblastoma, except for more visual disorders, an expected side-effect of the study drug.

CLINICAL TRIAL REGISTRATION

NCT02343406.

Informations de copyright

Copyright © 2021 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest statement Linda Dirven, Sarah Nuyens, Maarten Spruyt, Thierry Gorlia, Corneel Coens and Jaap C. Reijneveld have nothing to disclose. Paul M. J. Clement received study budget funds from AstraZeneca; was an advisory board member for AbbVie, AstraZeneca, BMS, Daiichi-Sankyo, Leo Pharma, Merck Serono, MSD and Vifor Pharma. Marica Eoli received consulting fees from AbbVie. Juan M. Sepulveda-Sanchez reports personal fees and non-financial support from AbbVie; a grant from Pfizer as principal investigator; personal fees and non-financial support from Celgene; non-financial support from Ipsen; and personal fees from Astellas. Annemiek M. E. Walenkamp received research grants from IPSEN and Novartis; was an advisory board member for IPSEN, Karyopharm, Novartis and Polyphor; and received study budget funds from AbbVie, BMS, Genzyme, Karyopharm Therapeutics and Roche. Jean Sebastien Frenel has received consulting fees from AstraZeneca, BIOCAD, Lilly, Novartis, Pfizer and Roche. Enrico Franceschi was an advisory board member for Celgene and Karyopharm. Michael Weller has received research grants from AbbVie, Adastra, Merck, Sharp & Dohme (MSD), Merck (EMD) and Novocure; and honoraria for lectures or advisory board participation or consulting from AbbVie, Basilea, Bristol Myers Squibb (BMS), Celgene, Medac, Merck, Sharp & Dohme (MSD), Merck (EMD), Nerviano Medical Sciences, Novartis, Orbus, Philogen, Roche and Tocagen. Olivier Chinot reports personal fees and non-financial support from Abbvie, during the conduct of the study; personal fees from immatics, non-financial support from BMS, non-financial support from Servier, grants, personal fees and non-financial support from Roche, outside the submitted work. Filip Y. F. L. De Vos received research grants from Novartis. Nicholas Whenham has received consulting fees from Bayer and Janssen. Paul Sanghera was an advisory board member for AbbVie and Roche. Jim Looman, Madan G. Kundu and Jan Peter de Geus are AbbVie employees and may own stock. Vassilis Golfinopoulos received research funding from AbbVie during the conduct of the study. Martin J. van den Bent received consulting fees from AbbVie, Agios, Bayer, Boston Pharmaceuticals, Carthera, Genenta, Karyopharm and Nerviano.