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

L. Gately; C. Mesía; J. M. Sepúlveda; S. del Barco; E. Pineda; R. Gironés; J. Fuster; W. Hong; M. Dumas; S. Gill; L. M. Navarro; A. Herrero; A. Dowling; R. de las Peñas; M. A. Vaz; M. Alonso; Z. Lwin; R. Harrup; S. Peralta; A. Long; P. Perez-Segura; E. Ahern; C. O. Garate; M. Wong; R. Campbell; K. Cuff; R. Jennens; O. Gallego; C. Underhill; M. Martinez-Garcia; M. Covela; A. Cooper; S. Brown; M. Rosenthal; J. Torres; I. M. Collins; P. Gibbs; C. Balana

doi:10.1007/s11060-023-04513-1

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

L. Gately
, C. Mesía
, J. M. Sepúlveda
, S. del Barco
, E. Pineda
, R. Gironés
, J. Fuster
, W. Hong
, M. Dumas
, S. Gill
, L. M. Navarro
, A. Herrero
, A. Dowling
, R. de las Peñas
, M. A. Vaz
, M. Alonso
, Z. Lwin
, R. Harrup
, S. Peralta
, A. Long

P. Perez-Segura, E. Ahern, C. O. Garate, M. Wong, R. Campbell, K. Cuff, R. Jennens, O. Gallego, C. Underhill, M. Martinez-Garcia, M. Covela, A. Cooper, S. Brown, M. Rosenthal, J. Torres, I. M. Collins, P. Gibbs, C. Balana

Walter and Eliza Hall Institute of Medical Research
Alfred Health
Institute Catala Oncologia
Hospital Universitario 12 de Octubre
Institut Català d’Oncologia Girona
Hospital Clínic de Barcelona
Hospital Universitario La Fe
Hospital Universitario Son Espases
Hospital de Salamanca
Hospital Miguel Servet
St. Vincent's Hospital Melbourne
Hospital Provincial de Castellón
Hospital Ramon y Cajal
Hospital Universitario Virgen del Rocio
Royal Brisbane and Women's Hospital
Royal Hobart Hospital
Hospital Sant Joan de Reus
Sir Charles Gairdner Hospital
Hospital Clínico San Carlos de Madrid
Monash Health
Fundacion Hospital Alcorcon
Westmead Hospital
Bendigo Health
Princess Alexandra Hospital
Epworth Health
Hospital de La Santa Creu I Sant Pau
Border Medical Oncology, Australia
Hospital del Mar
Hospital Lucus Augusti
Liverpool Hospital
Ballarat Health Services
Peter Maccallum Cancer Centre
Goulburn Valley Health
South West Regional Cancer Centre
Institut Investigació Germans Trias I Pujol (IGTP)

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

Abstract

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.
Correction to this title at https://doi.org/10.1007/s11060-024-04581-x

Original language	English
Pages (from-to)	407-415
Number of pages	9
Journal	Journal of Neuro-Oncology
Volume	166
Issue number	3
DOIs	https://doi.org/10.1007/s11060-023-04513-1
Publication status	Published - Feb 2024
Externally published	Yes

Keywords

Glioblastoma
Survival
Temozolomide

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10.1007/s11060-023-04513-1

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Gately, L., Mesía, C., Sepúlveda, J. M., del Barco, S., Pineda, E., Gironés, R., Fuster, J., Hong, W., Dumas, M., Gill, S., Navarro, L. M., Herrero, A., Dowling, A., de las Peñas, R., Vaz, M. A., Alonso, M., Lwin, Z., Harrup, R., Peralta, S., ... Balana, C. (2024). A combined analysis of two prospective randomised studies exploring the impact of extended post-radiation temozolomide on survival outcomes in newly diagnosed glioblastoma. Journal of Neuro-Oncology, 166(3), 407-415. https://doi.org/10.1007/s11060-023-04513-1

@article{226d7afcdea647b19447ba5d646a3738,

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

abstract = "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. Correction to this title at https://doi.org/10.1007/s11060-024-04581-x ",

keywords = "Glioblastoma, Survival, Temozolomide",

author = "L. Gately and C. Mes{\'i}a and Sep{\'u}lveda, \{J. M.\} and \{del Barco\}, S. and E. Pineda and R. Giron{\'e}s and J. Fuster and W. Hong and M. Dumas and S. Gill and Navarro, \{L. M.\} and A. Herrero and A. Dowling and \{de las Pe{\~n}as\}, R. and Vaz, \{M. A.\} and M. Alonso and Z. Lwin and R. Harrup and S. Peralta and A. Long and P. Perez-Segura and E. Ahern and Garate, \{C. O.\} and M. Wong and R. Campbell and K. Cuff and R. Jennens and O. Gallego and C. Underhill and M. Martinez-Garcia and M. Covela and A. Cooper and S. Brown and M. Rosenthal and J. Torres and Collins, \{I. M.\} and P. Gibbs and C. Balana",

year = "2024",

month = feb,

doi = "10.1007/s11060-023-04513-1",

language = "English",

volume = "166",

pages = "407--415",

journal = "Journal of Neuro-Oncology",

issn = "0167-594X",

publisher = "Springer",

number = "3",

}

Gately, L, Mesía, C, Sepúlveda, JM, del Barco, S, Pineda, E, Gironés, R, Fuster, J, Hong, W, Dumas, M, Gill, S, Navarro, LM, Herrero, A, Dowling, A, de las Peñas, R, Vaz, MA, Alonso, M, Lwin, Z, Harrup, R, Peralta, S, Long, A, Perez-Segura, P, Ahern, E, Garate, CO, Wong, M, Campbell, R, Cuff, K, Jennens, R, Gallego, O, Underhill, C, Martinez-Garcia, M, Covela, M, Cooper, A, Brown, S, Rosenthal, M, Torres, J, Collins, IM, Gibbs, P & Balana, C 2024, 'A combined analysis of two prospective randomised studies exploring the impact of extended post-radiation temozolomide on survival outcomes in newly diagnosed glioblastoma', Journal of Neuro-Oncology, vol. 166, no. 3, pp. 407-415. https://doi.org/10.1007/s11060-023-04513-1

TY - JOUR

T1 - A combined analysis of two prospective randomised studies exploring the impact of extended post-radiation temozolomide on survival outcomes in newly diagnosed glioblastoma

AU - Gately, L.

AU - Mesía, C.

AU - Sepúlveda, J. M.

AU - del Barco, S.

AU - Pineda, E.

AU - Gironés, R.

AU - Fuster, J.

AU - Hong, W.

AU - Dumas, M.

AU - Gill, S.

AU - Navarro, L. M.

AU - Herrero, A.

AU - Dowling, A.

AU - de las Peñas, R.

AU - Vaz, M. A.

AU - Alonso, M.

AU - Lwin, Z.

AU - Harrup, R.

AU - Peralta, S.

AU - Long, A.

AU - Perez-Segura, P.

AU - Ahern, E.

AU - Garate, C. O.

AU - Wong, M.

AU - Campbell, R.

AU - Cuff, K.

AU - Jennens, R.

AU - Gallego, O.

AU - Underhill, C.

AU - Martinez-Garcia, M.

AU - Covela, M.

AU - Cooper, A.

AU - Brown, S.

AU - Rosenthal, M.

AU - Torres, J.

AU - Collins, I. M.

AU - Gibbs, P.

AU - Balana, C.

PY - 2024/2

Y1 - 2024/2

N2 - 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. Correction to this title at https://doi.org/10.1007/s11060-024-04581-x

AB - 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. Correction to this title at https://doi.org/10.1007/s11060-024-04581-x

KW - Glioblastoma

KW - Survival

KW - Temozolomide

UR - https://www.scopus.com/pages/publications/85180655140

UR - https://go.openathens.net/redirector/westernsydney.edu.au?url=https://doi.org/10.1007/s11060-023-04513-1

U2 - 10.1007/s11060-023-04513-1

DO - 10.1007/s11060-023-04513-1

M3 - Article

C2 - 38153582

AN - SCOPUS:85180655140

SN - 0167-594X

VL - 166

SP - 407

EP - 415

JO - Journal of Neuro-Oncology

JF - Journal of Neuro-Oncology

IS - 3

ER -

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

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