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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: | open |
| Online Access: | PDF Full Text (PDF, 2.7 MB) |
| Persistent link: | http://urn.fi/urn:nbn:fi-fe2020051938347 |
| Language: | English |
| Published: |
Elsevier,
2020
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| Publish Date: | 2021-03-12 |
| Description: |
AbstractObjectives: 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). see all
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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/. |
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https://creativecommons.org/licenses/by-nc-nd/4.0/ |