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Real-world analysis of MET exon 14 mutations in non-small cell lung cancer : a retrospective study from two Swedish hospitals

Skribek, Marcus ; Brunnström, Hans LU orcid ; Oskarsdottir, Gudrun LU ; Portu Grivé, Mikel ; Aricak, Ozan ; Planck, Maria LU ; Jatta, Kenbugul ; Naserhojati, Homeyra ; Haglund de Flon, Felix and Ekman, Simon (2023) In Acta Oncologica 62(12). p.1808-1814
Abstract

Background: Real-World evidence on mesenchymal-epithelial transition exon 14 skipping mutations (METex14) in lung cancer remains limited. With an incidence of 3–4% across histological subtypes, METex14 is now an actionable target for MET inhibitors (METi) in advanced lung cancer, demonstrating response rates between 30–70%. Yet, its role in early stages and sensitivity to immune checkpoint inhibitors (ICIs) is still under exploration. Material and methods: We conducted a retrospective analysis of the clinical data of lung cancer patients presenting with METex14 across all stages. These patients were treated at two Swedish University Hospitals: Karolinska and Skåne, between the years 2014 and 2022. Results: We identified a total of 63... (More)

Background: Real-World evidence on mesenchymal-epithelial transition exon 14 skipping mutations (METex14) in lung cancer remains limited. With an incidence of 3–4% across histological subtypes, METex14 is now an actionable target for MET inhibitors (METi) in advanced lung cancer, demonstrating response rates between 30–70%. Yet, its role in early stages and sensitivity to immune checkpoint inhibitors (ICIs) is still under exploration. Material and methods: We conducted a retrospective analysis of the clinical data of lung cancer patients presenting with METex14 across all stages. These patients were treated at two Swedish University Hospitals: Karolinska and Skåne, between the years 2014 and 2022. Results: We identified a total of 63 patients, of which 50 met the inclusion criteria. The median overall survival (OS) with corresponding 95% confidence intervals (95% CI) according to the stage was not reached (NR) for stage I, NR for stage II, 15 months (95% CI, 5.4–24.6) for stage III, and 17 months (95% CI, 9.2–NR) for stage IV. The median OS for stage IV patients who received a METi was 17 months (95% CI, 9.5–NR) vs. 10 months (95% CI, 6.2–NR) in patients without METi (p = 0.92; Hazard Ratio [HR] = 1.07). The median OS for stage IV patients who received ICIs was 18 months (95% CI, 16.5–NR) vs. 6 months (95% CI, 2.5–NR) in patients without ICIs (p = 0.15; HR = 0.47). The median OS for stage IV patients who received chemotherapy was 17 months (95% CI, 9.7–NR) vs. 10 months (95% CI, 4.5–NR) in patients without (p = 0.97; HR = 0.98). Conclusions: Our data suggest limited survival benefits from METi, ICIs, and chemotherapy for METex14 lung cancer patients. While not statistically significant, these findings underscore the need for larger trials for validation. Identifying effective treatments for this challenging lung cancer subtype remains a priority.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
chemotherapy, immune checkpoint inhibitors, Lung cancer, MET exon 14 skipping mutations, MET inhibitors
in
Acta Oncologica
volume
62
issue
12
pages
7 pages
publisher
Taylor & Francis
external identifiers
  • pmid:37897706
  • scopus:85175376095
ISSN
0284-186X
DOI
10.1080/0284186X.2023.2269310
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
id
0cb8653e-ddbd-4ccc-977b-3bbfcc7dc6eb
date added to LUP
2023-12-13 14:31:14
date last changed
2024-04-12 06:19:59
@article{0cb8653e-ddbd-4ccc-977b-3bbfcc7dc6eb,
  abstract     = {{<p>Background: Real-World evidence on mesenchymal-epithelial transition exon 14 skipping mutations (METex14) in lung cancer remains limited. With an incidence of 3–4% across histological subtypes, METex14 is now an actionable target for MET inhibitors (METi) in advanced lung cancer, demonstrating response rates between 30–70%. Yet, its role in early stages and sensitivity to immune checkpoint inhibitors (ICIs) is still under exploration. Material and methods: We conducted a retrospective analysis of the clinical data of lung cancer patients presenting with METex14 across all stages. These patients were treated at two Swedish University Hospitals: Karolinska and Skåne, between the years 2014 and 2022. Results: We identified a total of 63 patients, of which 50 met the inclusion criteria. The median overall survival (OS) with corresponding 95% confidence intervals (95% CI) according to the stage was not reached (NR) for stage I, NR for stage II, 15 months (95% CI, 5.4–24.6) for stage III, and 17 months (95% CI, 9.2–NR) for stage IV. The median OS for stage IV patients who received a METi was 17 months (95% CI, 9.5–NR) vs. 10 months (95% CI, 6.2–NR) in patients without METi (p = 0.92; Hazard Ratio [HR] = 1.07). The median OS for stage IV patients who received ICIs was 18 months (95% CI, 16.5–NR) vs. 6 months (95% CI, 2.5–NR) in patients without ICIs (p = 0.15; HR = 0.47). The median OS for stage IV patients who received chemotherapy was 17 months (95% CI, 9.7–NR) vs. 10 months (95% CI, 4.5–NR) in patients without (p = 0.97; HR = 0.98). Conclusions: Our data suggest limited survival benefits from METi, ICIs, and chemotherapy for METex14 lung cancer patients. While not statistically significant, these findings underscore the need for larger trials for validation. Identifying effective treatments for this challenging lung cancer subtype remains a priority.</p>}},
  author       = {{Skribek, Marcus and Brunnström, Hans and Oskarsdottir, Gudrun and Portu Grivé, Mikel and Aricak, Ozan and Planck, Maria and Jatta, Kenbugul and Naserhojati, Homeyra and Haglund de Flon, Felix and Ekman, Simon}},
  issn         = {{0284-186X}},
  keywords     = {{chemotherapy; immune checkpoint inhibitors; Lung cancer; MET exon 14 skipping mutations; MET inhibitors}},
  language     = {{eng}},
  number       = {{12}},
  pages        = {{1808--1814}},
  publisher    = {{Taylor & Francis}},
  series       = {{Acta Oncologica}},
  title        = {{Real-world analysis of MET exon 14 mutations in non-small cell lung cancer : a retrospective study from two Swedish hospitals}},
  url          = {{http://dx.doi.org/10.1080/0284186X.2023.2269310}},
  doi          = {{10.1080/0284186X.2023.2269310}},
  volume       = {{62}},
  year         = {{2023}},
}