Temozolomide and Radiotherapy versus Radiotherapy Alone in Patients with Glioblastoma, <i>IDH</i>-wildtype: <i>Post Hoc</i> Analysis of the EORTC Randomized Phase III CATNON Trial-Reference-Cited by-同舟云学术

Temozolomide and Radiotherapy versus Radiotherapy Alone in Patients with Glioblastoma, IDH-wildtype: Post Hoc Analysis of the EORTC Randomized Phase III CATNON Trial

Published:2022-03-11 Issue:12 Volume:28 Page:2527-2535
ISSN:1078-0432
Container-title:Clinical Cancer Research
language:en
Short-container-title:

Author:

Tesileanu C. Mircea S.¹^ORCID,Sanson Marc²^ORCID,Wick Wolfgang³^ORCID,Brandes Alba A.⁴,Clement Paul M.⁵^ORCID,Erridge Sara C.⁶,Vogelbaum Michael A.⁷,Nowak Anna K.⁸⁹¹⁰^ORCID,Baurain Jean-Francois¹¹^ORCID,Mason Warren P.¹²,Wheeler Helen¹³^ORCID,Chinot Olivier L.¹⁴^ORCID,Gill Sanjeev¹⁵,Griffin Matthew¹⁶,Rogers Leland¹⁷,Taal Walter¹^ORCID,Rudà Roberta¹⁸,Weller Michael¹⁹^ORCID,McBain Catherine²⁰,van Linde Myra E.²¹,Aldape Kenneth¹²^ORCID,Jenkins Robert B.²²,Kros Johan M.²³^ORCID,Wesseling Pieter²⁴²⁵^ORCID,von Deimling Andreas²⁶^ORCID,Hoogstrate Youri¹^ORCID,de Heer Iris¹,Atmodimedjo Peggy N.²³,Dubbink Hendrikus J.²³^ORCID,Brouwer Rutger W.W.²⁷,van IJcken Wilfred F.J.²⁷^ORCID,Cheung Kin Jip²⁸,Golfinopoulos Vassilis²⁸^ORCID,Baumert Brigitta G.²⁹³⁰,Gorlia Thierry²⁸,French Pim J.¹^ORCID,van den Bent Martin J.¹^ORCID

Affiliation:

1. 1Neurology Department, Brain Tumor Center, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.

2. 2Sorbonne Université, Inserm, CNRS, UMR S 1127, Paris Brain Institute – Institut du Cerveau (ICM), AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin, Paris, France.

3. 3Neurology Department, University of Heidelberg, and Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

4. 4Medical Oncology Department, AUSL-IRCCS Scienze Neurologiche, Bologna, Italy.

5. 5Oncology Department, KU Leuven and General Medical Oncology Department, UZ Leuven, Leuven Cancer Institute, Leuven, Belgium.

6. 6Edinburgh Centre for Neuro-Oncology, Western General Hospital, University of Edinburgh, Edinburgh, United Kingdom.

7. 7Neuro-Oncology Department, Moffitt Cancer Center, Tampa, Florida.

8. 8Medical School, University of Western Australia, Crawley, Western Australia.

9. 9Medical Oncology Department, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, Western Australia.

10. 10CoOperative Group for NeuroOncology, University of Sydney, New South Wales, Australia.

11. 11Medical Oncology Department, King Albert II Cancer Institute, Cliniques universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.

12. 12Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada.

13. 13Northern Sydney Cancer Centre, University of Sydney, St Leonards, New South Wales, Australia.

14. 14Aix-Marseille University, AP-HM, Neuro-Oncology division, Marseille, France.

15. 15Medical Oncology Department, Alfred Hospital, Melbourne, Australia.

16. 16Clinical Oncology Department, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom.

17. 17Radiation Oncology Department, Gammawest Cancer Services, Salt Lake City, Utah.

18. 18Neuro-Oncology Department, City of Health and Science Hospital and University of Turin, Turin, Italy.

19. 19Neurology Department, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland.

20. 20Clinical Oncology Department, The Christie NHS FT, Manchester, United Kingdom.

21. 21Medical Oncology Department, Brain Tumor Center Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.

22. 22Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.

23. 23Pathology Department, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.

24. 24Pathology Department, Amsterdam University Medical Centers, Amsterdam, the Netherlands.

25. 25Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.

26. 26Neuropathology Department, Ruprecht-Karls-University, and CCU Neuropathology German Cancer Institute and Consortium, DKFZ, and DKTK, Heidelberg, Germany.

27. 27Center for Biomics, Erasmus MC, Rotterdam, the Netherlands.

28. 28EORTC HQ, Brussels, Belgium.

29. 29Radiation-Oncology Department (MAASTRO), Maastricht University Medical Center (MUMC) and GROW (School for Oncology), Maastricht, the Netherlands.

30. 30Institute of Radiation-Oncology, Cantonal Hospital Graubünden, Chur, Switzerland.

Abstract

Abstract Purpose: In a post hoc analysis of the CATNON trial (NCT00626990), we explored whether adding temozolomide to radiotherapy improves outcome in patients with IDH1/2 wildtype (wt) anaplastic astrocytomas with molecular features of glioblastoma [redesignated as glioblastoma, isocitrate dehydrogenase–wildtype (IDH-wt) in the 2021 World Health Organization (WHO) classification of central nervous system tumors]. Patients and Methods: From the randomized phase III CATNON study examining the addition of adjuvant and concurrent temozolomide to radiotherapy in anaplastic astrocytomas, we selected a subgroup of IDH1/2wt and H3F3Awt tumors with presence of TERT promoter mutations and/or EGFR amplifications and/or combined gain of chromosome 7 and loss of chromosome 10. Molecular abnormalities including MGMT promoter methylation status were determined by next-generation sequencing, DNA methylation profiling, and SNaPshot analysis. Results: Of the 751 patients entered in the CATNON study, 670 had fully molecularly characterized tumors. A total of 159 of these tumors met the WHO 2021 molecular criteria for glioblastoma, IDH-wt. Of these patients, 47 received radiotherapy only and 112 received a combination of radiotherapy and temozolomide. There was no added effect of temozolomide on either overall survival [HR, 1.19; 95% confidence interval (CI), 0.82–1.71] or progression-free survival (HR, 0.87; 95% CI, 0.61–1.24). MGMT promoter methylation was prognostic for overall survival, but was not predictive for outcome to temozolomide treatment either with respect to overall survival or progression-free survival. Conclusions: In this cohort of patients with glioblastoma, IDH-wt temozolomide treatment did not add benefit beyond that observed from radiotherapy, regardless of MGMT promoter status. These findings require a new well-powered prospective clinical study to explore the efficacy of temozolomide treatment in this patient population.

Funder

NRG

Cancer Research UK

Cancer Australia

Publisher

American Association for Cancer Research (AACR)

Subject

Cancer Research,Oncology

Link

https://aacrjournals.org/clincancerres/article-pdf/doi/10.1158/1078-0432.CCR-21-4283/3055374/ccr-21-4283.pdf

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