University of Oulu

Eide IJZ, Stensgaard S, Helland Å, Ekman S, Mellemgaard A, Hansen KH, Cicenas S, Koivunen J, Grønberg BH, Sørensen BS, Brustugun OT. Osimertinib in non-small cell lung cancer with uncommon EGFR-mutations: a post-hoc subgroup analysis with pooled data from two phase II clinical trials. Transl Lung Cancer Res 2022;11(6):953-963. doi: 10.21037/tlcr-21-9

Osimertinib in non-small cell lung cancer with uncommon EGFR-mutations : a post-hoc subgroup analysis with pooled data from two phase II clinical trials

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Author: Eide, Inger Johanne Zwicky1,2,3; Stensgaard, Simone4; Helland, Åslaug2,3,5;
Organizations: 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
3Institute of Clinical Medicine, University of Oslo, Oslo, Norway
4Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
5Department of Oncology, Oslo University Hospital, Oslo, Norway
6Department of Oncology-Pathology, Karolinska Institutet, Thoracic Oncology Center, Karolinska University Hospital, Stockholm, Sweden
7Herlev Hospital, Copenhagen, Denmark
8Odense University Hospital, Odense, Denmark
9National Cancer Institute, Vilnius University Faculty of Medicine, Vilnius, Lithuania
10Oulu University Hospital, University of Oulu, Medical Research Center Oulu, Oulu, Finland
11Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
12Department of Oncology, St. Olav’s Hospital, Trondheim University Hospital, Trondheim, Norway
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.8 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2023062965858
Language: English
Published: AME Publishing Company, 2022
Publish Date: 2023-06-29
Description:

Abstract

Background: Osimertinib is standard of care for EGFR-mutated non-small cell lung cancer (NSCLC) patients. The efficacy of the drug in patients with mutations other than the common deletion in exon 19 and L858R in exon 21 is largely unknown.

Methods: We identified patients with uncommon EGFR-mutations from two prospective clinical phase II, single-arm studies for previously treated patients and untreated patients, respectively, and pooled data for this analysis. All patients received treatment with osimertinib 80 mg daily until radiological progression or death. The primary endpoint of both trials was objective response rate (ORR), with progression-free survival (PFS), overall survival (OS) and intracranial efficacy as key secondary endpoints. Circulating tumour DNA (ctDNA) was analysed before and two weeks after treatment initiation in the first line cohort.

Results: Of 299 enrolled patients in the two trials, 21 patients with uncommon mutations were identified; 12 patients had a single mutation (G719X or L861Q), one patient had L861Q and an exon 20 insertion, and 8 patients had compound mutations with G719X and either L861Q or S768I. Three of the 10 pretreated patients had the T790M resistance mutation. ORR was 47.6% and disease control rate (DCR) 85.7%. The median duration of response (DoR) was 7.9 months. Among 11 patients treated with osimertinib in first line, ORR was 63.6% vs. 30.0% of 10 previously treated patients. The median PFS was 5.5 months in both groups. Patients with G719X-compound mutations had a higher response rate (62.5% vs. 38.5%), a longer median PFS (13.7 vs. 3.5 months) and median OS (29.3 vs. 7.5 months) than patients with other mutations. Most first line treated patients (81.8%) displayed a reduction in ctDNA after two weeks of treatment.

Conclusions: Osimertinib demonstrates activity in patients with uncommon EGFR-mutations, and especially for G719X-compound mutations.

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Series: Translational lung cancer research
ISSN: 2218-6751
ISSN-E: 2226-4477
ISSN-L: 2218-6751
Volume: 11
Issue: 6
Pages: 953 - 963
DOI: 10.21037/tlcr-21-995
OADOI: https://oadoi.org/10.21037/tlcr-21-995
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Subjects:
Funding: This work was supported by AstraZeneca (Nos. ESR-14-10267 and D5161C00007) and the South-Eastern Norway Regional Health Authority (Nos. 2021012 to IJZE and 2018049 to OTB).
Copyright information: © Translational Lung Cancer Research. All rights reserved. This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
  https://creativecommons.org/licenses/by-nc-nd/4.0/