TY - JOUR
T1 - 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
AU - Clement, Paul M J
AU - Dirven, Linda
AU - Eoli, Marica
AU - Sepulveda-Sanchez, Juan M
AU - Walenkamp, Annemiek M E
AU - Frenel, Jean S
AU - Franceschi, Enrico
AU - Weller, Michael
AU - Chinot, Olivier
AU - De Vos, Filip Y F L
AU - Whenham, Nicolas
AU - Sanghera, Paul
AU - Looman, Jim
AU - Kundu, Madan G
AU - Peter de Geus, Jan
AU - Nuyens, Sarah
AU - Spruyt, Maarten
AU - Gorlia, Thierry
AU - Coens, Corneel
AU - Golfinopoulos, Vassilis
AU - Reijneveld, Jaap C
AU - van den Bent, Martin J
N1 - Funding Information:
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.We are grateful to AbbVie for supporting this independent EORTC study. We thank Arijit Ganguli for his contribution in the development of this manuscript. We thank Alan Saltzman of Fishawack Facilitate Ltd, part of Fishawack Health, for medical writing support (funded by AbbVie).
Funding Information:
This is an independent EORTC study that was funded by AbbVie Inc. The contributions of the authors acting on behalf of EORTC and AbbVie Inc., are listed below. All authors contributed to the development of the publication and maintained control over the final content.
Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/4
Y1 - 2021/4
N2 - 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/m2, Depatux-M alone, or TMZ or oral lomustine (CCNU) 110 mg/m2 (TMZ/CCNU). HRQoL outcomes were recorded using the EORTC core Quality of Life QLQ-C30, and brain cancer-specific QLQ-BN20 questionnaires. Questionnaires were completed at baseline, weeks 8 and 16, and month 6, and changes from baseline to each time point were calculated. NDFS was defined as time to first deterioration in World Health Organisation performance status.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.
AB - 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/m2, Depatux-M alone, or TMZ or oral lomustine (CCNU) 110 mg/m2 (TMZ/CCNU). HRQoL outcomes were recorded using the EORTC core Quality of Life QLQ-C30, and brain cancer-specific QLQ-BN20 questionnaires. Questionnaires were completed at baseline, weeks 8 and 16, and month 6, and changes from baseline to each time point were calculated. NDFS was defined as time to first deterioration in World Health Organisation performance status.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.
KW - Depatuxizumab mafodotin
KW - Glioblastoma
KW - Lomustine
KW - Patient-reported outcomes
KW - Phase II
KW - Quality of life
KW - Randomised
KW - Temozolomide
KW - Visual disorders
UR - http://www.scopus.com/inward/record.url?scp=85101039639&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2021.01.010
DO - 10.1016/j.ejca.2021.01.010
M3 - Article
C2 - 33601293
SN - 0959-8049
VL - 147
SP - 1
EP - 12
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -