Role of next generation sequencing-based liquid biopsy in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors: impact of STK11, KRAS and TP53 mutations and co-mutations on outcome.
Immunotherapy
STK11
circulating tumor DNA
lung cancer
predictive biomarkers
Journal
Translational lung cancer research
ISSN: 2218-6751
Titre abrégé: Transl Lung Cancer Res
Pays: China
ID NLM: 101646875
Informations de publication
Date de publication:
Jan 2021
Jan 2021
Historique:
entrez:
11
2
2021
pubmed:
12
2
2021
medline:
12
2
2021
Statut:
ppublish
Résumé
Characterization of tumor-related genetic alterations is promising for the screening of new predictive markers in non-small cell lung cancer (NSCLC). Aim of the study was to evaluate prognostic and predictive role of most frequent tumor-associated genetic alterations detected in plasma before starting immune checkpoint inhibitors (ICIs). Between January 2017 and October 2019, advanced NSCLC patients were prospectively screened with plasma next-generation sequencing (NGS) while included in two trials: VISION (NCT02864992), using Guardant360 A total of 103 patients receiving ICIs were analyzed: median overall survival (OS) was 20.8 (95% CI: 16.7-24.9) months and median immune-related progression free disease (irPFS) 4.2 (95% CI: 2.3-6.1) months. TP53 mutations in plasma negatively affected OS both in patients treated with ICIs and in control group (P=0.001 and P=0.009), indicating a prognostic role. STK11 mutated patients (n=9) showed a trend for worse OS only if treated with ICIs. The presence of KRAS/STK11 co-mutation and KRAS/STK11/TP53 co-mutation affected OS only in patients treated with ICIs (HR =10.936, 95% CI: 2.337-51.164, P=0.002; HR =17.609, 95% CI: 3.777-82.089, P<0.001, respectively), indicating a predictive role. Plasma genotyping demonstrated prognostic value of TP53 mutations and predictive value of KRAS/STK11 and KRAS/STK11/TP53 co-mutations.
Sections du résumé
BACKGROUND
BACKGROUND
Characterization of tumor-related genetic alterations is promising for the screening of new predictive markers in non-small cell lung cancer (NSCLC). Aim of the study was to evaluate prognostic and predictive role of most frequent tumor-associated genetic alterations detected in plasma before starting immune checkpoint inhibitors (ICIs).
METHODS
METHODS
Between January 2017 and October 2019, advanced NSCLC patients were prospectively screened with plasma next-generation sequencing (NGS) while included in two trials: VISION (NCT02864992), using Guardant360
RESULTS
RESULTS
A total of 103 patients receiving ICIs were analyzed: median overall survival (OS) was 20.8 (95% CI: 16.7-24.9) months and median immune-related progression free disease (irPFS) 4.2 (95% CI: 2.3-6.1) months. TP53 mutations in plasma negatively affected OS both in patients treated with ICIs and in control group (P=0.001 and P=0.009), indicating a prognostic role. STK11 mutated patients (n=9) showed a trend for worse OS only if treated with ICIs. The presence of KRAS/STK11 co-mutation and KRAS/STK11/TP53 co-mutation affected OS only in patients treated with ICIs (HR =10.936, 95% CI: 2.337-51.164, P=0.002; HR =17.609, 95% CI: 3.777-82.089, P<0.001, respectively), indicating a predictive role.
CONCLUSIONS
CONCLUSIONS
Plasma genotyping demonstrated prognostic value of TP53 mutations and predictive value of KRAS/STK11 and KRAS/STK11/TP53 co-mutations.
Identifiants
pubmed: 33569305
doi: 10.21037/tlcr-20-674
pii: tlcr-10-01-202
pmc: PMC7867770
doi:
Types de publication
Journal Article
Langues
eng
Pagination
202-220Informations de copyright
2021 Translational Lung Cancer Research. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-20-674). RR serves as a current Editor-in-chief for Translational Lung Cancer Research. The other authors have no conflicts of interest to declare.
Références
Ann Oncol. 2019 Aug 1;30(8):1321-1328
pubmed: 31125062
N Engl J Med. 2018 Nov 22;379(21):2040-2051
pubmed: 30280635
Immunotargets Ther. 2018 Jul 31;7:63-75
pubmed: 30105218
Carcinogenesis. 2014 Mar;35(3):546-53
pubmed: 24170201
Lung Cancer. 2019 Apr;130:50-58
pubmed: 30885352
Cancer Med. 2020 Apr;9(7):2343-2351
pubmed: 32022477
Oncol Rep. 2020 Aug;44(2):424-437
pubmed: 32627031
Cancer Immunol Immunother. 2019 Oct;68(10):1621-1633
pubmed: 31549213
Cancer Discov. 2018 Jul;8(7):822-835
pubmed: 29773717
Science. 2015 Apr 3;348(6230):124-8
pubmed: 25765070
Immunotherapy. 2016;8(3):299-313
pubmed: 26865127
ESMO Open. 2020 May;5(3):e000748
pubmed: 32467099
Lancet. 2016 Apr 9;387(10027):1540-1550
pubmed: 26712084
PLoS One. 2009;4(4):e5137
pubmed: 19340305
JCO Precis Oncol. 2019;3:
pubmed: 31428721
PLoS Med. 2007 Oct 16;4(10):e296
pubmed: 17941714
EMBO J. 2004 Feb 25;23(4):833-43
pubmed: 14976552
Nature. 2019 Nov;575(7782):294-295
pubmed: 31705127
Blood. 2003 Jun 15;101(12):4878-86
pubmed: 12586633
Nature. 2007 Aug 16;448(7155):807-10
pubmed: 17676035
J Clin Oncol. 2014 Feb 20;32(6):579-86
pubmed: 24449238
Gastroenterology. 2010 Aug;139(2):586-97, 597.e1-6
pubmed: 20452353
N Engl J Med. 2020 Sep 3;383(10):931-943
pubmed: 32469185
PLoS One. 2012;7(9):e45877
pubmed: 23029290
Nat Med. 2017 Jun;23(6):703-713
pubmed: 28481359
Clin Cancer Res. 2000 Oct;6(10):4055-63
pubmed: 11051256
PLoS Med. 2006 Oct;3(10):e420
pubmed: 17020408
J Thorac Oncol. 2018 Sep;13(9):1248-1268
pubmed: 29885479
Oncotarget. 2016 Nov 8;7(45):73389-73401
pubmed: 27705915
N Engl J Med. 2016 Nov 10;375(19):1823-1833
pubmed: 27718847
J Thorac Oncol. 2015 Mar;10(3):431-7
pubmed: 25415430
Clin Cancer Res. 2018 Jan 15;24(2):334-340
pubmed: 29089357
Nat Rev Immunol. 2015 Dec;15(12):760-70
pubmed: 26603901
Lung Cancer. 2020 Feb;140:42-45
pubmed: 31862576
Lancet. 2017 Jan 21;389(10066):255-265
pubmed: 27979383
Nature. 2019 Nov;575(7781):217-223
pubmed: 31666701
Nat Rev Clin Oncol. 2013 Aug;10(8):437-50
pubmed: 23799370
Mol Med Rep. 2014 Mar;9(3):1019-24
pubmed: 24469340
Biomol Detect Quantif. 2019 Mar 18;17:100087
pubmed: 30923679
Nat Rev Cancer. 2009 Aug;9(8):563-75
pubmed: 19629071
Lung Cancer. 2017 Oct;112:62-68
pubmed: 29191602
N Engl J Med. 2015 Oct 22;373(17):1627-39
pubmed: 26412456
Oncotarget. 2019 Mar 5;10(19):1840-1849
pubmed: 30956762
J Clin Oncol. 2020 May 10;38(14):1608-1632
pubmed: 31990617
Biomark Res. 2020 Aug 26;8:34
pubmed: 32864131
Sci Transl Med. 2014 Feb 19;6(224):224ra24
pubmed: 24553385
Science. 2018 Oct 12;362(6411):
pubmed: 30309915
Oncogene. 2008 Nov 24;27(55):6908-19
pubmed: 19029933
Ann Oncol. 2018 Oct 1;29(Suppl 4):iv192-iv237
pubmed: 30285222
Clin Cancer Res. 2002 Jul;8(7):2085-90
pubmed: 12114407
PLoS One. 2019 Apr 25;14(4):e0215381
pubmed: 31022191
Nat Commun. 2019 Jul 17;10(1):3143
pubmed: 31316060
Mol Cell. 2006 Mar 3;21(5):689-700
pubmed: 16507366
J Clin Oncol. 2008 Jul 20;26(21):3543-51
pubmed: 18506025
Br J Cancer. 2020 Jul;123(1):81-91
pubmed: 32376889
Lung Cancer. 2019 Nov;137:1-6
pubmed: 31518912
Oncotarget. 2015 May 20;6(14):12783-95
pubmed: 25904052
N Engl J Med. 2019 Nov 21;381(21):2020-2031
pubmed: 31562796
N Engl J Med. 2018 May 31;378(22):2078-2092
pubmed: 29658856
Cancer Discov. 2015 Aug;5(8):860-77
pubmed: 26069186
Lancet Oncol. 2019 Jul;20(7):924-937
pubmed: 31122901
J Thorac Oncol. 2021 Nov;16(11):1883-1892
pubmed: 34265431
Lung Cancer. 2018 Sep;123:70-75
pubmed: 30089598
Int J Mol Sci. 2019 Apr 16;20(8):
pubmed: 30995715
N Engl J Med. 2015 Jul 9;373(2):123-35
pubmed: 26028407
J Clin Oncol. 2018 Mar 1;36(7):633-641
pubmed: 29337640
J Thorac Oncol. 2019 Nov;14(11):1881-1883
pubmed: 31668314
Br J Cancer. 2009 Jan 27;100(2):370-5
pubmed: 19165201
Clin Cancer Res. 2017 Jul 1;23(13):3316-3324
pubmed: 28119362
Nat Med. 2008 Sep;14(9):985-90
pubmed: 18670422
JAMA Oncol. 2018 Nov 1;4(11):1543-1552
pubmed: 30193240
Oncogene. 2011 Sep 1;30(35):3784-91
pubmed: 21532627
Cancer Discov. 2019 Jan;9(1):34-45
pubmed: 30297358
Nat Rev Cancer. 2019 Mar;19(3):133-150
pubmed: 30755690