Correlations between pathogenic variants in DNA repair genes and anticancer treatment efficacy in stage IV non-small cell lung cancer: A large real-world cohort and review of the literature.
DNA damage repair mutations
immunotherapy
non-small cell lung cancer
platinum-based chemotherapy
radiotherapy
Journal
Thoracic cancer
ISSN: 1759-7714
Titre abrégé: Thorac Cancer
Pays: Singapore
ID NLM: 101531441
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
revised:
01
04
2023
received:
07
02
2023
accepted:
03
04
2023
medline:
14
6
2023
pubmed:
25
4
2023
entrez:
24
04
2023
Statut:
ppublish
Résumé
Mutations in genes involved in DNA damage repair (DDR), a hallmark of cancer, are associated with increased cancer cell sensitivity to certain therapies. This study sought to evaluate the association of DDR pathogenic variants with treatment efficacy in patients with advanced non-small cell lung cancer (NSCLC). A retrospective cohort of consecutive patients with advanced NSCLC attending a tertiary medical center who underwent next-generation sequencing in 01/2015-8/2020 were clustered according to DDR gene status and compared for overall response rate (ORR), progression-free survival (PFS) (patients receiving systemic therapy), local PFS (patients receiving definitive radiotherapy), and overall survival (OS) using log-rank and Cox regression analyses. Of 225 patients with a clear tumor status, 42 had a pathogenic/likely pathogenic DDR variant (pDDR), and 183 had no DDR variant (wtDDR). Overall survival was similar in the two groups (24.2 vs. 23.1 months, p = 0.63). The pDDR group had a higher median local PFS after radiotherapy (median 45 months vs. 9.9 months, respectively; p = 0.044), a higher ORR (88.9% vs. 36.2%, p = 0.04), and a longer median PFS (not reached vs. 6.0 months, p = 0.01) in patients treated with immune checkpoint blockade. There was no difference in ORR, median PFS, and median OS in patients treated with platinum-based chemotherapy. Our retrospective data suggest that in patients with stage 4 NSCLC, pathogenic variants in DDR pathway genes may be associated with higher efficacy of radiotherapy and immune checkpoint inhibitors (ICIs). This should be further explored prospectively.
Sections du résumé
BACKGROUND
Mutations in genes involved in DNA damage repair (DDR), a hallmark of cancer, are associated with increased cancer cell sensitivity to certain therapies. This study sought to evaluate the association of DDR pathogenic variants with treatment efficacy in patients with advanced non-small cell lung cancer (NSCLC).
METHODS
A retrospective cohort of consecutive patients with advanced NSCLC attending a tertiary medical center who underwent next-generation sequencing in 01/2015-8/2020 were clustered according to DDR gene status and compared for overall response rate (ORR), progression-free survival (PFS) (patients receiving systemic therapy), local PFS (patients receiving definitive radiotherapy), and overall survival (OS) using log-rank and Cox regression analyses.
RESULTS
Of 225 patients with a clear tumor status, 42 had a pathogenic/likely pathogenic DDR variant (pDDR), and 183 had no DDR variant (wtDDR). Overall survival was similar in the two groups (24.2 vs. 23.1 months, p = 0.63). The pDDR group had a higher median local PFS after radiotherapy (median 45 months vs. 9.9 months, respectively; p = 0.044), a higher ORR (88.9% vs. 36.2%, p = 0.04), and a longer median PFS (not reached vs. 6.0 months, p = 0.01) in patients treated with immune checkpoint blockade. There was no difference in ORR, median PFS, and median OS in patients treated with platinum-based chemotherapy.
CONCLUSION
Our retrospective data suggest that in patients with stage 4 NSCLC, pathogenic variants in DDR pathway genes may be associated with higher efficacy of radiotherapy and immune checkpoint inhibitors (ICIs). This should be further explored prospectively.
Identifiants
pubmed: 37095004
doi: 10.1111/1759-7714.14902
pmc: PMC10260479
doi:
Substances chimiques
Immune Checkpoint Inhibitors
0
Types de publication
Review
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1589-1596Informations de copyright
© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Références
Science. 2001 Feb 16;291(5507):1284-9
pubmed: 11181991
Thorac Cancer. 2023 Jun;14(17):1589-1596
pubmed: 37095004
Cancer Discov. 2017 Jul;7(7):675-693
pubmed: 28630051
PLoS One. 2011;6(5):e20055
pubmed: 21647442
J Thorac Oncol. 2017 Nov;12(11):1673-1678
pubmed: 28843361
Lung Cancer. 2011 Jun;72(3):370-7
pubmed: 21075476
Gene. 2014 Apr 1;538(2):361-5
pubmed: 24368330
JCO Precis Oncol. 2020;4:355-366
pubmed: 32856010
Clin Cancer Res. 2020 Aug 1;26(15):4135-4142
pubmed: 32332016
Cell Mol Life Sci. 2020 Feb;77(4):677-703
pubmed: 31612241
Radiother Oncol. 2015 Oct;117(1):77-82
pubmed: 26253951
Adv Radiat Oncol. 2020 Nov 14;6(1):100615
pubmed: 33665490
Front Immunol. 2021 Sep 24;12:708558
pubmed: 34630387
Biomed Res Int. 2020 Oct 22;2020:3520764
pubmed: 33150172
Oral Oncol. 2014 Mar;50(3):234-9
pubmed: 24387978
N Engl J Med. 2016 Nov 10;375(19):1823-1833
pubmed: 27718847
Clin Cancer Res. 2017 Jul 15;23(14):3610-3618
pubmed: 28137924
JAMA Netw Open. 2019 Sep 4;2(9):e1911895
pubmed: 31539077
N Engl J Med. 2019 Jul 25;381(4):317-327
pubmed: 31157963
Swiss Med Wkly. 2011 Oct 19;141:w13275
pubmed: 22009704
N Engl J Med. 2018 Dec 27;379(26):2495-2505
pubmed: 30345884
Lancet Oncol. 2020 Jan;21(1):162-174
pubmed: 31806540
Nature. 2013 Oct 17;502(7471):333-339
pubmed: 24132290
J Clin Oncol. 2018 Jun 10;36(17):1685-1694
pubmed: 29489427
Sci Rep. 2016 Dec 14;6:39217
pubmed: 27966655
Gynecol Oncol. 2020 Jul;158(1):66-76
pubmed: 32402633
Lancet. 2019 May 4;393(10183):1819-1830
pubmed: 30955977
N Engl J Med. 2018 Aug 23;379(8):753-763
pubmed: 30110579
Lung Cancer. 2007 May;56(2):281-8
pubmed: 17222938
Clin Cancer Res. 2019 Aug 1;25(15):4701-4711
pubmed: 31068370
J Mol Diagn. 2015 May;17(3):251-64
pubmed: 25801821
J Oncol. 2020 Jun 24;2020:3132786
pubmed: 32684929