University of Oulu

Inger Johanne Zwicky Eide, Åslaug Helland, Simon Ekman, Anders Mellemgaard, Karin Holmskov Hansen, Saulius Cicenas, Jussi Koivunen, Bjørn Henning Grønberg, Odd Terje Brustugun, Osimertinib in T790M-positive and -negative patients with EGFR-mutated advanced non-small cell lung cancer (the TREM-study), Lung Cancer, Volume 143, 2020, Pages 27-35, ISSN 0169-5002, https://doi.org/10.1016/j.lungcan.2020.03.009

Osimertinib in T790M-positive and -negative patients with EGFR-mutated advanced non-small cell lung cancer (the TREM-study)

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Author: Zwicky Eide, Inger Johanne1,2; Helland, Åslaug2,3,4; Ekman, Simon5;
Organizations: 1Vestre Viken Hospital Trust, Drammen, Norway
2Department of Cancer Genetics, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
3Departement of Oncology, Oslo University Hospital, Oslo, Norway
4University of Oslo, Department of Clinical Medicine, Oslo, Norway
5Thoracic Oncology Center, Karolinska University Hospital/Departement of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
6Odense University Hospital, Odense, Denmark
7National Cancer Institute, VU MF, Vilnius, Lithuania
8Oulu University Hospital, University of Oulu, MRC Oulu, Oulu, Finland
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
Format: article
Version: accepted version
Access: embargoed
Persistent link: http://urn.fi/urn:nbn:fi-fe2020051938347
Language: English
Published: Elsevier, 2020
Publish Date: 2021-03-12
Description:

Abstract

Objectives: In non-small cell lung cancer patients with acquired resistance to first- or second-generation EGFR-TKIs, osimertinib is approved in the presence of the T790 M resistance mutation. We assessed the efficacy of osimertinib in both T790M-positive and T790M-negative patients.

Materials and methods: The TREM-study is an investigator-initiated, multi-centre, single-arm, phase 2 clinical trial conducted in five Northern European countries. Patients with progression on at least one previous EGFR-TKI were assigned to treatment with 80 mg of osimertinib daily until radiological progression or death. Patients were included regardless of the presence of T790 M. The primary endpoint was objective response rate (ORR).

Results: Of 199 included patients, 120 (60 %) were T790M-positive, 52 (26 %) were T790M-negative and 27 (14 %) had unknown T790M-status. 24 % had brain metastases and 15 % had an ECOG performance status of 2. Overall ORR was 48 % (95 % CI, 41 %–55 %), 60 % (51 %–69 %) for T790M-positive patients and 28 % (15 %–41 %) for T790M-negative patients, p < 0.001. ORR for patients with co-occurring del19 vs L858R was 61 % vs 32 %, p = 0.001. Duration of response was similar between the T790M-positive and –negative groups (11.8 vs 10.7 months, p = 0.229). Overall median progression-free survival (PFS) was 8.9 months (95 % CI, 7.4–10.5), and 10.8 vs 5.1 months for T790M-positive vs –negative patients (HR 0.62, p = 0.007). Median overall survival (OS) was 17.9 months (95 % CI, 14.4–21.3). For T790M-positive vs –negative median OS was 22.5 vs 13.4 months, (HR 0.55, p = 0.002).

Conclusions: This study confirms the efficacy of osimertinib for T790M-positive patients. There was also clinically significant activity of osimertinib in a proportion of T790M-negative patients.

Clinical trial registration: This trial is registered with ClinicalTrials.gov (NCT02504346).

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Series: Lung cancer
ISSN: 0169-5002
ISSN-E: 1872-8332
ISSN-L: 0169-5002
Volume: 143
Pages: 27 - 35
DOI: 10.1016/j.lungcan.2020.03.009
OADOI: https://oadoi.org/10.1016/j.lungcan.2020.03.009
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Subjects:
Funding: The trial received economic support from AstraZeneca and the South-Eastern Norway Regional Health Authority. The study drug was provided by AstraZeneca.
Copyright information: © 2020 Elsevier B.V. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/.
  https://creativecommons.org/licenses/by-nc-nd/4.0/