Predictive value of p53 and AXL immunostaining for the efficacy of immune checkpoint inhibitor-based therapy after osimertinib treatment in patients with epidermal growth factor-mutant non-small cell lung cancer.

Humans Carcinoma, Non-Small-Cell Lung / drug therapy Epidermal Growth Factor ErbB Receptors / genetics Immune Checkpoint Inhibitors / therapeutic use Lung Neoplasms / drug therapy Mutation Neoplasm Recurrence, Local Protein Kinase Inhibitors / therapeutic use Retrospective Studies Tumor Suppressor Protein p53 / genetics
AXL EGFR mutation Immune checkpoint inhibitor Non-small cell lung cancer p53

Journal

Cancer immunology, immunotherapy : CII
ISSN: 1432-0851
Titre abrégé: Cancer Immunol Immunother
Pays: Germany
ID NLM: 8605732

Informations de publication

Date de publication:
Jun 2023
Historique:
received: 11 08 2022
accepted: 05 01 2023
medline: 22 5 2023
pubmed: 9 1 2023
entrez: 8 1 2023
Statut: ppublish

Résumé

Current evidence indicates that immune checkpoint inhibitors (ICIs) have a limited efficacy in patients with lung cancer harboring epidermal growth factor receptor (EGFR) mutations. However, there is a lack of data on the efficacy of ICIs after osimertinib treatment, and the predictors of ICI efficacy are unclear. We retrospectively assessed consecutive patients with EGFR-mutant NSCLC who received ICI-based therapy after osimertinib treatment at 10 institutions in Japan, between March 2016 and March 2021. Immunohistochemical staining was used to evaluate the expression of p53 and AXL. The deletions of exon 19 and the exon 21 L858R point mutation in EGFR were defined as common mutations; other mutations were defined as uncommon mutations. A total of 36 patients with advanced or recurrent EGFR-mutant NSCLC were analyzed. In multivariate analysis, p53 expression in tumors was an independent predictor of PFS after ICI-based therapy (p = 0.002). In patients with common EGFR mutations, high AXL expression was a predictor of shorter PFS and overall survival after ICI-based therapy (log-rank test; p = 0.04 and p = 0.02, respectively). The levels of p53 in pretreatment tumors may be a predictor of ICI-based therapy outcomes in patients with EGFR-mutant NSCLC after osimertinib treatment. High levels of AXL in tumors may also be a predictor of ICI-based therapy outcomes, specifically for patients with common EGFR mutations. Further prospective large-scale investigations on the predictors of ICI efficacy following osimertinib treatment are warranted.

Sections du résumé

BACKGROUND BACKGROUND
Current evidence indicates that immune checkpoint inhibitors (ICIs) have a limited efficacy in patients with lung cancer harboring epidermal growth factor receptor (EGFR) mutations. However, there is a lack of data on the efficacy of ICIs after osimertinib treatment, and the predictors of ICI efficacy are unclear.
METHODS METHODS
We retrospectively assessed consecutive patients with EGFR-mutant NSCLC who received ICI-based therapy after osimertinib treatment at 10 institutions in Japan, between March 2016 and March 2021. Immunohistochemical staining was used to evaluate the expression of p53 and AXL. The deletions of exon 19 and the exon 21 L858R point mutation in EGFR were defined as common mutations; other mutations were defined as uncommon mutations.
RESULTS RESULTS
A total of 36 patients with advanced or recurrent EGFR-mutant NSCLC were analyzed. In multivariate analysis, p53 expression in tumors was an independent predictor of PFS after ICI-based therapy (p = 0.002). In patients with common EGFR mutations, high AXL expression was a predictor of shorter PFS and overall survival after ICI-based therapy (log-rank test; p = 0.04 and p = 0.02, respectively).
CONCLUSION CONCLUSIONS
The levels of p53 in pretreatment tumors may be a predictor of ICI-based therapy outcomes in patients with EGFR-mutant NSCLC after osimertinib treatment. High levels of AXL in tumors may also be a predictor of ICI-based therapy outcomes, specifically for patients with common EGFR mutations. Further prospective large-scale investigations on the predictors of ICI efficacy following osimertinib treatment are warranted.

Identifiants

DOI: 10.1007/s00262-023-03370-1 PMID: 36617602
pubmed: 36617602
doi: 10.1007/s00262-023-03370-1
pii: 10.1007/s00262-023-03370-1
doi:

Substances chimiques

Epidermal Growth Factor 62229-50-9
ErbB Receptors EC 2.7.10.1
Immune Checkpoint Inhibitors 0
osimertinib 3C06JJ0Z2O
Protein Kinase Inhibitors 0
Tumor Suppressor Protein p53 0
AXL protein, human 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1699-1707

Informations de copyright

© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Références

Maemondo M, Inoue A, Kobayashi K et al (2010) Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 362(25):2380–2388. https://doi.org/10.1056/NEJMoa0909530
doi: 10.1056/NEJMoa0909530 pubmed: 20573926
Mitsudomi T, Morita S, Yatabe Y et al (2010) Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 11(2):121–128. https://doi.org/10.1016/S1470-2045(09)70364-X
doi: 10.1016/S1470-2045(09)70364-X pubmed: 20022809
Sequist LV, Yang JC, Yamamoto N et al (2013) Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 31(27):3327–3334. https://doi.org/10.1200/JCO.2012.44.2806
doi: 10.1200/JCO.2012.44.2806 pubmed: 23816960
Soria JC, Ohe Y, Vansteenkiste J et al (2018) Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med 378(2):113–125. https://doi.org/10.1056/NEJMoa1713137
doi: 10.1056/NEJMoa1713137 pubmed: 29151359
Ramalingam SS, Vansteenkiste J, Planchard D et al (2020) Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med 382(1):41–50. https://doi.org/10.1056/NEJMoa1913662
doi: 10.1056/NEJMoa1913662 pubmed: 31751012
Passaro A, Leighl N, Blackhall F et al (2022) ESMO expert consensus statements on the management of EGFR mutant non-small-cell lung cancer. Ann Oncol S0923–7534:00112. https://doi.org/10.1016/j.annonc.2022.02.003
doi: 10.1016/j.annonc.2022.02.003
Mazieres J, Drilon A, Lusque A et al (2019) Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry. Ann Oncol 30:1321–1328. https://doi.org/10.1093/annonc/mdz167
doi: 10.1093/annonc/mdz167 pubmed: 31125062 pmcid: 7389252
Morimoto K, Sawada R, Yamada T et al (2022) A real-world analysis of immune checkpoint inhibitor-based therapy after osimertinib treatment in EGFR-mutant non-small cell lung cancer patients. JTO Clin Res Rep 3(9):100388. https://doi.org/10.1016/j.jtocrr.2022.100388
doi: 10.1016/j.jtocrr.2022.100388 pubmed: 36082280 pmcid: 9445370
Hong S, Gao F, Fu S et al (2018) Concomitant genetic alterations with response to treatment and epidermal growth factor receptor tyrosine kinase inhibitors in patients with EGFR-mutant advanced non-small cell lung cancer. JAMA Oncol 4(5):739–742. https://doi.org/10.1001/jamaoncol.2018.0049
doi: 10.1001/jamaoncol.2018.0049 pubmed: 29596544 pmcid: 5885210
Kim Y, Lee B, Shim JH et al (2019) Concurrent genetic alterations predict the progression to target therapy in EGFR-mutated advanced NSCLC. J Thorac Oncol 14(2):193–202. https://doi.org/10.1016/j.jtho.2018.10.150
doi: 10.1016/j.jtho.2018.10.150 pubmed: 30391576
Nahar R, Zhai W, Zhang T et al (2018) Elucidating the genomic architecture of Asian EGFR-mutant lung adenocarcinoma through multi-region exome sequencing. Nat Commun 9(1):216. https://doi.org/10.1038/s41467-017-02584-z
doi: 10.1038/s41467-017-02584-z pubmed: 29335443 pmcid: 5768770
Guo Y, Song J, Wang Y et al (2020) Concurrent genetic alterations and other biomarkers predict treatment efficacy of EGFR-TKIs in EGFR-mutant non-small cell lung cancer: a review. Front Oncol 10:610923. https://doi.org/10.3389/fonc.2020.610923
doi: 10.3389/fonc.2020.610923 pubmed: 33363040 pmcid: 7758444
Yoshimura A, Yamada T, Serizawa M et al (2022) High levels of AXL expression in untreated EGFR-mutated NSCLC negatively impacts the use of osimertinib. Cancer Sci. https://doi.org/10.1111/cas.15608 . https://doi.org/10.1111/cas.15608. [published online ahead of print, 2022 Sep 28]
Offin M, Chan JM, Tenet M et al (2019) Concurrent RB1 and TP53 alterations define a subset of EGFR-mutant lung cancers at risk for histologic transformation and inferior clinical outcomes. J Thorac Oncol 14(10):1784–1793. https://doi.org/10.1016/j.jtho.2019.06.002
doi: 10.1016/j.jtho.2019.06.002 pubmed: 31228622 pmcid: 6764905
Singh N, Piskorz AM, Bosse T et al (2020) p53 immunohistochemistry is an accurate surrogate for TP53 mutational analysis in endometrial carcinoma biopsies. J Pathol 250(3):336–345. https://doi.org/10.1002/path.5375
doi: 10.1002/path.5375 pubmed: 31829441
Hwang HJ, Nam SK, Park H et al (2020) Prediction of TP53 mutations by p53 immunohistochemistry and their prognostic significance in gastric cancer. J Pathol Transl Med 54(5):378–386. https://doi.org/10.4132/jptm.2020.06.01
doi: 10.4132/jptm.2020.06.01 pubmed: 32601264 pmcid: 7483024
Antony J, Huang RY (2017) AXL-driven EMT state as a targetable conduit in cancer. Cancer Res 77(14):3725–3732. https://doi.org/10.1158/0008-5472.CAN-17-0392
doi: 10.1158/0008-5472.CAN-17-0392 pubmed: 28667075
Graham DK, DeRyckere D, Davies KD, Earp HS (2014) The TAM family: phosphatidylserine sensing receptor tyrosine kinases gone awry in cancer. Nat Rev Cancer 14(12):769–785. https://doi.org/10.1038/nrc3847
doi: 10.1038/nrc3847 pubmed: 25568918
Holland SJ, Powell MJ, Franci C et al (2005) Multiple roles for the receptor tyrosine kinase axl in tumor formation. Cancer Res 65(20):9294–9303. https://doi.org/10.1158/0008-5472.CAN-05-0993
doi: 10.1158/0008-5472.CAN-05-0993 pubmed: 16230391
Okura N, Nishioka N, Yamada T et al (2020) ONO-7475, a novel AXL inhibitor, suppresses the adaptive resistance to initial EGFR-TKI treatment in EGFR-mutated non-small cell lung cancer. Clin Cancer Res 26(9):2244–2256. https://doi.org/10.1158/1078-0432.CCR-19-2321
doi: 10.1158/1078-0432.CCR-19-2321 pubmed: 31953310
Taniguchi H, Yamada T, Wang R et al (2019) AXL confers intrinsic resistance to osimertinib and advances the emergence of tolerant cells. Nat Commun 10(1):259. https://doi.org/10.1038/s41467-018-08074-0
doi: 10.1038/s41467-018-08074-0 pubmed: 30651547 pmcid: 6335418
Kanda Y (2013) Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transplant 48(3):452–458. https://doi.org/10.1038/bmt.2012.244
doi: 10.1038/bmt.2012.244 pubmed: 23208313
Yamada T, Hirai S, Katayama Y et al (2019) Retrospective efficacy analysis of immune checkpoint inhibitors in patients with EGFR-mutated non-small cell lung cancer. Cancer Med 8(4):1521–1529. https://doi.org/10.1002/cam4.2037
doi: 10.1002/cam4.2037 pubmed: 30790471 pmcid: 6488155
Lin S, Li X, Lin M, Yue W (2021) Meta-analysis of P53 expression and sensitivity to platinum-based chemotherapy in patients with non-small cell lung cancer. Medicine 100(5):e24194
doi: 10.1097/MD.0000000000024194 pubmed: 33592864 pmcid: 7870161
Dong ZY, Zhong WZ, Zhang XC et al (2017) Potential predictive value of TP53 and KRAS mutation status for response to PD-1 blockade immunotherapy in lung adenocarcinoma. Clin Cancer Res 23(12):3012–3024. https://doi.org/10.1158/1078-0432.CCR-16-2554
doi: 10.1158/1078-0432.CCR-16-2554 pubmed: 28039262
Assoun S, Theou-Anton N, Nguenang M et al (2019) Association of TP53 mutations with response and longer survival under immune checkpoint inhibitors in advanced non-small-cell lung cancer. Lung Cancer 132:65–71. https://doi.org/10.1016/j.lungcan.2019.04.005
doi: 10.1016/j.lungcan.2019.04.005 pubmed: 31097096
Biton J, Mansuet-Lupo A, Pécuchet N et al (2018) TP53, STK11, and EGFR mutations predict tumor immune profile and the response to anti-PD-1 in lung adenocarcinoma. Clin Cancer Res 24(22):5710–5723. https://doi.org/10.1158/1078-0432.CCR-18-0163
doi: 10.1158/1078-0432.CCR-18-0163 pubmed: 29764856
Isomoto K, Haratani K, Hayashi H et al (2020) Impact of EGFR-TKI treatment on the tumor immune microenvironment in EGFR mutation-positive non-small cell lung cancer. Clin Cancer Res 26(8):2037–2046. https://doi.org/10.1158/1078-0432.CCR-19-2027
doi: 10.1158/1078-0432.CCR-19-2027 pubmed: 31937613
Köbel M, Piskorz AM, Lee S et al (2016) Optimized p53 immunohistochemistry is an accurate predictor of TP53 mutation in ovarian carcinoma. J Pathol Clin Res 2(4):247–258. https://doi.org/10.1002/cjp2.53
doi: 10.1002/cjp2.53 pubmed: 27840695 pmcid: 5091634
Engelsen AST, Lotsberg ML, AbouKhouzam R et al (2022) Dissecting the role of AXL in cancer immune escape and resistance to immune checkpoint inhibition. Front Immunol 13:869676. https://doi.org/10.3389/fimmu.2022.869676
doi: 10.3389/fimmu.2022.869676 pubmed: 35572601 pmcid: 9092944
Lee W, Kim DK, Synn CB et al (2022) Incorporation of SKI-G-801, a novel AXL inhibitor, with anti-PD-1 plus chemotherapy improves anti-tumor activity and survival by enhancing T cell immunity. Front Oncol 12:821391. https://doi.org/10.3389/fonc.2022.821391
doi: 10.3389/fonc.2022.821391 pubmed: 35356198 pmcid: 8959645
Synn CB, Kim SE, Lee HK et al (2021) SKI-G-801, an AXL kinase inhibitor, blocks metastasis through inducing anti-tumor immune responses and potentiates anti-PD-1 therapy in mouse cancer models. Clin Transl Immunol 11(1):e1364. https://doi.org/10.1002/cti2.1364
doi: 10.1002/cti2.1364
Goyette MA, Elkholi IE, Apcher C et al (2021) Targeting Axl favors an antitumorigenic microenvironment that enhances immunotherapy responses by decreasing Hif-1α levels. Proc Natl Acad Sci USA 118(29):e2023868118. https://doi.org/10.1073/pnas.2023868118
doi: 10.1073/pnas.2023868118 pubmed: 34266948 pmcid: 8307381

Auteurs

Kenji Morimoto (K)

Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kajii-Cho, Kamigyo-Ku, Kyoto, Japan.

Tadaaki Yamada (T)

Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kajii-Cho, Kamigyo-Ku, Kyoto, Japan. tayamada@koto.kpu-m.ac.jp.

Ryo Sawada (R)

Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kajii-Cho, Kamigyo-Ku, Kyoto, Japan.

Koichi Azuma (K)

Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Fukuoka City, Japan.

Yasuhiro Goto (Y)

Department of Respiratory Medicine, Fujita Health University School of Medicine, Aichi, Japan.

Taishi Harada (T)

Department of Medical Oncology, Fukuchiyama City Hospital, Kyoto, Japan.

Shinsuke Shiotsu (S)

Department of Respiratory Medicine, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan.

Nobuyo Tamiya (N)

Department of Pulmonary Medicine, Rakuwakai Otowa Hospital, Kyoto, Japan.

Yusuke Chihara (Y)

Department of Respiratory Medicine, Uji-Tokushukai Medical Center, Kyoto, Japan.

Takayuki Takeda (T)

Department of Respiratory Medicine, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan.

Osamu Hiranuma (O)

Department of Pulmonary Medicine, Otsu City Hospital, Shiga, Japan.

Isao Hasegawa (I)

Department of Pulmonary Medicine, Saiseikai Shiga Hospital, Shiga, Japan.

Satomi Tanaka (S)

Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kajii-Cho, Kamigyo-Ku, Kyoto, Japan.

Akihiro Yoshimura (A)

Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kajii-Cho, Kamigyo-Ku, Kyoto, Japan.

Masahiro Iwasaku (M)

Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kajii-Cho, Kamigyo-Ku, Kyoto, Japan.

Shinsaku Tokuda (S)

Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kajii-Cho, Kamigyo-Ku, Kyoto, Japan.

Young Hak Kim (YH)

Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kajii-Cho, Kamigyo-Ku, Kyoto, Japan.

Koichi Takayama (K)

Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kajii-Cho, Kamigyo-Ku, Kyoto, Japan.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Predictive value of p53 and AXL immunostaining...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Tumeurs de l'appareil respiratoire › Tumeurs du poumon › Tumeurs des bronches › Carcinome bronchogénique › Carcinome pulmonaire non à petites cellules › Predictive value of p53 and AXL immunostaining...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Protéines de la famille de l'EGF › Facteur de croissance épidermique › Predictive value of p53 and AXL immunostaining...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs peptidiques › Récepteur facteur croissance › Récepteurs ErbB › Predictive value of p53 and AXL immunostaining...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › Antinéoplasiques immunologiques › Inhibiteurs de points de contrôle immunitaires › Predictive value of p53 and AXL immunostaining...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Tumeurs de l'appareil respiratoire › Tumeurs du poumon › Predictive value of p53 and AXL immunostaining...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Predictive value of p53 and AXL immunostaining...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Récidive tumorale locale › Predictive value of p53 and AXL immunostaining...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antienzymes › Inhibiteurs de protéines kinases › Predictive value of p53 and AXL immunostaining...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études rétrospectives › Predictive value of p53 and AXL immunostaining...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Phosphoprotéines › Protéine p53 suppresseur de tumeur › Predictive value of p53 and AXL immunostaining...