A combined analysis of two prospective randomised studies exploring the impact of extended post-radiation temozolomide on survival outcomes in newly diagnosed glioblastoma.

Autor: Gately L; Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia. gately.l@wehi.edu.au.; Department of Medical Oncology, Alfred Health, Melbourne, VIC, Australia. gately.l@wehi.edu.au., Mesía C; Medical Oncology Service, Institut Català d'Oncologia, Hospitalet de Llobregat, Barcelona, Spain., Sepúlveda JM; Medical Oncology Service, Hospital Universitario 12 de Octubre, Madrid, Spain., Del Barco S; Medical Oncology Service, Institut Català d'Oncologia Girona, Girona, Spain., Pineda E; Medical Oncology Service, Hospital Clinic de Barcelona, Barcelona, Spain., Gironés R; Medical Oncology Service, Hospital Universitario La Fe, Valencia, Spain., Fuster J; Medical Oncology Service, Hospital Son Espases, Palma de Mallorca, Spain., Hong W; Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia., Dumas M; Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia., Gill S; Department of Medical Oncology, Alfred Health, Melbourne, VIC, Australia., Navarro LM; Medical Oncology Service, Hospital de Salamanca, Salamanca, Spain., Herrero A; Medical Oncology Service, Hospital Miguel Servet, Zaragoza, Spain., Dowling A; Department of Medical Oncology, St Vincent's Hospital Melbourne, Melbourne, VIC, Australia., de Las Peñas R; Medical Oncology Service, Hospital Provincial de Castellón, Castellón, Spain., Vaz MA; Medical Oncology Service, Hospital Ramón y Cajal, Madrid, Spain., Alonso M; Medical Oncology Service, Hospital Virgen del Rocio, Seville, Spain., Lwin Z; Department of Medical Oncology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia., Harrup R; Department of Medical Oncology, Royal Hobart Hospital, Hobart, TAS, Australia., Peralta S; Medical Oncology Service, Hospital Sant Joan de Reus, Reus, Spain., Long A; Department of Medical Oncology, Sir Charles Gairdner Hospital, Perth, WA, Australia., Perez-Segura P; Medical Oncology Service, Hospital Clinico San Carlos, Madrid, Spain., Ahern E; Department of Medical Oncology, Monash Health, Melbourne, VIC, Australia., Garate CO; Medical Oncology Service, Hospital Universitario Fundación Alcorcón, Alcorcón, Spain., Wong M; Department of Medical Oncology, Westmead Hospital, Westmead, NSW, Australia., Campbell R; Department of Medical Oncology, Bendigo Health, Bendigo, VIC, Australia., Cuff K; Department of Medical Oncology, Princess Alexandra Hospital, Brisbane, QLD, Australia., Jennens R; Department of Medical Oncology, Epworth Health, Richmond, VIC, Australia., Gallego O; Medical Oncology Service, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain., Underhill C; Department of Medical Oncology, Border Medical Oncology, East Albury, NSW, Australia., Martinez-Garcia M; Medical Oncology Service, Hospital del Mar, Barcelona, Spain., Covela M; Medical Oncology Service, Hospital Lucus Augusti, Lugo, Spain., Cooper A; Department of Medical Oncology, Liverpool Hospital, Liverpool, NSW, Australia., Brown S; Department of Medical Oncology, Ballarat Health Services, Ballarat, VIC, Australia., Rosenthal M; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia., Torres J; Department of Medical Oncology, Goulburn Valley Health, Shepparton, VIC, Australia., Collins IM; Department of Medical Oncology, South West Regional Cancer Centre, Geelong, VIC, Australia., Gibbs P; Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia., Balana C; Medical Oncology Service, Institut Català d'Oncologia, Badalona, Spain.; Badalona Applied Research Group in Oncology (B-ARGO), Institut Investigació Germans Trias i Pujol (IGTP), Badalona, Spain.
Jazyk: angličtina
Zdroj: Journal of neuro-oncology [J Neurooncol] 2024 Feb; Vol. 166 (3), pp. 407-415. Date of Electronic Publication: 2023 Dec 28.
DOI: 10.1007/s11060-023-04513-1
Abstrakt: Purpose: The optimal duration of post-radiation temozolomide in newly diagnosed glioblastoma remains unclear, with no published phase III randomised trials. Standard-of-care stipulates 6 months. However, in routine care, it is often extended to 12 months, despite lacking robust supporting data.
Methods: GEINO14-01 (Spain) and EX-TEM (Australia) studies enrolled glioblastoma patients without progression at the end of 6 months post-radiation temozolomide. Participants were randomised 1:1 to six additional months of temozolomide or observation. Primary endpoint was 6-month progression free survival from date of randomisation (6mPFS). Secondary endpoints included overall survival (OS) and toxicity. 204 patients were required to detect an improvement in 6mPFS from 50 to 60% (80% power). Neither study recruited sufficient patients. We performed a combined analysis of individual patient data.
Results: 205 patients were recruited: 159 in GEINO14-01 (2014-2018) and 46 in EX-TEM (2019-2022). Median follow-up was 20.0 and 14.5 months. Baseline characteristics were balanced. There was no significant improvement in 6mPFS (57.2% vs 64.0%, OR0.75, p = 0.4), nor across any subgroups, including MGMT methylated; PFS (HR0.92, p = 0.59, median 7.8 vs 9.7 months); or OS (HR1.03, p = 0.87, median 20.1 vs 19.4 months). During treatment extension, 64% experienced any grade adverse event, mainly fatigue and gastrointestinal (both 54%). Only a minority required treatment changes: 4.5% dose delay, 7.5% dose reduction, 1.5% temozolomide discontinuation.
Conclusion: For glioblastoma patients, extending post-radiation temozolomide from 6 to 12 months is well tolerated but does not improve 6mPFS. We could not identify any subset that benefitted from extended treatment. Six months should remain standard-of-care.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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