Inger Johanne Zwicky Eide, Harald Grut, Åslaug Helland, Simon Ekman, Jens Benn Sørensen, Karin Holmskov Hansen, Bjørn Henning Grønberg, Saulius Cicenas, Jussi Pekka Koivunen, Anders Mellemgaard & Odd Terje Brustugun (2021) Intracranial effect of osimertinib in relapsed EGFR-mutated T790M-positive and -negative non-small cell lung cancer patients: results from a phase II study, Acta Oncologica, 60:12, 1565-1571, DOI: 10.1080/0284186X.2021.1973092
Intracranial effect of osimertinib in relapsed EGFR-mutated T790M-positive and -negative non-small cell lung cancer patients: results from a phase II study
|Author:||Eide, Inger Johanne Zwicky1,2,3; Grut, Harald4; Helland, Åslaug2,3,5;|
1Section of Oncology, Vestre Viken Hospital Trust, Drammen, Norway
2Department of Cancer Genetics, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
3Department of Clinical Medicine, University of Oslo, Oslo, Norway
4Department of Radiology, Vestre Viken Hospital Trust, Drammen, Norway
5Department of Oncology, Oslo University Hospital, Oslo, Norway
6Thoracic Oncology Center, Karolinska University Hospital/Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
7Rigshospitalet, Copenhagen, Denmark
8Odense University Hospital, Odense, Denmark
9Department of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway
10Department of Oncology, St. Olav’s Hospital, Trondheim University Hospital, Trondheim, Norway
11National Cancer Institute, VU MF, Vilnius, Lithuania
12Oulu University Hospital, University of Oulu, Oulu, Finland
13Herlev Hospital, Copenhagen, Denmark
|Online Access:||PDF Full Text (PDF, 0.7 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2023030730294
|Publish Date:|| 2023-03-07
Introduction: Osimertinib is effective for relapsed T790M-positive patients with brain metastases. The high brain permeability suggests that also such patients without T790M could benefit. Therefore, we evaluated the effect of osimertinib on brain metastases in both T790M-positive and -negative patients.
Methods: The TREM-study was an investigator-initiated phase II, single-arm, multi-institutional clinical trial conducted in Northern Europe. Patients with resistance to prior EGFR-TKIs received osimertinib until radiological progression, unacceptable toxicity or death. Baseline brain scans were performed in patients with known or suspected brain metastases and repeated every 8–12 weeks. We assessed intracranial efficacy in patients with baseline brain metastases.
Results: Brain metastases were detected in 48/199 patients at baseline. Of these, 63% were T790M-positive, 27% -negative and 10% had unknown T790M-status. The majority (73%) of the patients had received prior whole brain radiotherapy and additionally 8% had received stereotactic radiosurgery (SRS). Brain scans were available for review for 42 patients. The intracranial progression free survival was 39.7 versus 3.5 months for T790M + and T790M- patients, respectively (p < 0.001). The overall intracranial disease control rate (iDCR) was 81%, and for T790M + and T790M- patients the DCR was 89% versus 55%, respectively. The estimated risk of CNS progression was 0.8% at 6 months and 6% at 12 months for T790M-positive patients, and 14% and 17% at 6 and 12 months, respectively, for the T790M-negative.
Conclusions: This subgroup analysis confirms CNS efficacy of osimertinib in patients with the T790M resistance mutation, while other treatment options should be considered for EGFR-TKI relapsed T790M-negative patients with brain metastases.
|Pages:||1565 - 1571|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
This work was supported by AstraZeneca under grant number ESR-14-10267; the South-Eastern Norway Regional Health Authority under research grant number 2021012 to I. J. Z. E. and research grant no 2018049 to O. T. B. The study drug was provided by AstraZeneca. The funding sources did not have any role in the collection of data, analyses or interpretation of the results, nor did they participate in writing of the manuscript.
© 2021 Acta Oncologica Foundation. This is an Accepted Manuscript version of the following article, accepted for publication in Acta Oncologica. Inger Johanne Zwicky Eide, Harald Grut, Åslaug Helland, Simon Ekman, Jens Benn Sørensen, Karin Holmskov Hansen, Bjørn Henning Grønberg, Saulius Cicenas, Jussi Pekka Koivunen, Anders Mellemgaard & Odd Terje Brustugun (2021) Intracranial effect of osimertinib in relapsed EGFR-mutated T790M-positive and -negative non-small cell lung cancer patients: results from a phase II study, Acta Oncologica, 60:12, 1565-1571, DOI: 10.1080/0284186X.2021.1973092. It is deposited under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.