Prognostic Impact of TP53 Mutations in Metastatic Nonsquamous Non-small-cell Lung Cancer
The prognostic impact of TP53 mutations in advanced or metastatic nonsquamous non-small-cell lung cancer (nsNSCLC) patients treated with chemotherapy and/or immune checkpoint inhibitors (ICI) remains unclear. We retrospectively collected data from patients with nsNSCLC treated in the first line from...
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| Veröffentlicht in: | Clinical lung cancer 2024-05, Vol.25 (3), p.244-253.e2 |
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| creator | Mathiot, Laurent Nigen, Benoit Goronflot, Thomas Hiret, Sandrine Doucet, Ludovic Pons-Tostivint, Elvire Bennouna, Jaafar Denis, Marc G Herbreteau, Guillaume Raimbourg, Judith |
| description | The prognostic impact of TP53 mutations in advanced or metastatic nonsquamous non-small-cell lung cancer (nsNSCLC) patients treated with chemotherapy and/or immune checkpoint inhibitors (ICI) remains unclear.
We retrospectively collected data from patients with nsNSCLC treated in the first line from January 2018 to May 2021. The patient was separated into 2 groups according to their TP53 mutation status (wt vs. mut). Survival was estimated through the Kaplan-Meier method and compared by log-rank test.
Of 220 patients included, 126 were in the mutTP53 group, and 94 were in the wtTP53wt group. Median OS (mOS) was not significantly different between the mutTP53 and wtTP53 groups [17.5 months (95% confidence interval (CI), 11.3-21.5) vs. 9.5 months (95% CI, 7.4-14.2), (P = .051)]. In subgroup analyses, the mutTP53 group treated with ICI had a significantly improved mOS compared to the wtTP53 group [(24.7 months (95% CI, 20.8-not reach) vs. 12.0 months (95% CI, 4.7-not reach), (P = .017)] and mPFS [(9.6 months (95% CI, 5.8-not reach) vs. 3.2 months (95% CI, 1.3-13.8) (P = .048)]. There was no difference in terms of mOS and mPFS between the mutTP53 and the wtTP53 group treated by chemotherapy alone or combined with ICI.
TP53 mutation had no survival impact in the overall population, but is associated with better outcomes with ICI alone. These results suggest that patients with TP53 mutations could be treated with ICI alone, and wild-type patients could benefit from the addition of chemotherapy. |
| doi_str_mv | 10.1016/j.cllc.2023.12.004 |
| format | Article |
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We retrospectively collected data from patients with nsNSCLC treated in the first line from January 2018 to May 2021. The patient was separated into 2 groups according to their TP53 mutation status (wt vs. mut). Survival was estimated through the Kaplan-Meier method and compared by log-rank test.
Of 220 patients included, 126 were in the mutTP53 group, and 94 were in the wtTP53wt group. Median OS (mOS) was not significantly different between the mutTP53 and wtTP53 groups [17.5 months (95% confidence interval (CI), 11.3-21.5) vs. 9.5 months (95% CI, 7.4-14.2), (P = .051)]. In subgroup analyses, the mutTP53 group treated with ICI had a significantly improved mOS compared to the wtTP53 group [(24.7 months (95% CI, 20.8-not reach) vs. 12.0 months (95% CI, 4.7-not reach), (P = .017)] and mPFS [(9.6 months (95% CI, 5.8-not reach) vs. 3.2 months (95% CI, 1.3-13.8) (P = .048)]. There was no difference in terms of mOS and mPFS between the mutTP53 and the wtTP53 group treated by chemotherapy alone or combined with ICI.
TP53 mutation had no survival impact in the overall population, but is associated with better outcomes with ICI alone. These results suggest that patients with TP53 mutations could be treated with ICI alone, and wild-type patients could benefit from the addition of chemotherapy.</description><identifier>ISSN: 1525-7304</identifier><identifier>ISSN: 1938-0690</identifier><identifier>EISSN: 1938-0690</identifier><identifier>DOI: 10.1016/j.cllc.2023.12.004</identifier><identifier>PMID: 38218680</identifier><language>eng</language><publisher>United States: Elsevier</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Carcinoma, Non-Small-Cell Lung - drug therapy ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - mortality ; Carcinoma, Non-Small-Cell Lung - pathology ; Female ; Humans ; Immune Checkpoint Inhibitors - therapeutic use ; Life Sciences ; Lung Neoplasms - drug therapy ; Lung Neoplasms - genetics ; Lung Neoplasms - mortality ; Lung Neoplasms - pathology ; Male ; Middle Aged ; Mutation ; Prognosis ; Retrospective Studies ; Survival Rate ; Tumor Suppressor Protein p53 - genetics</subject><ispartof>Clinical lung cancer, 2024-05, Vol.25 (3), p.244-253.e2</ispartof><rights>Copyright © 2023. Published by Elsevier Inc.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c340t-59ae67aca7c9f6a42f291e31ea34a31c96d2ce161a5c37383235bf77c275cd583</citedby><cites>FETCH-LOGICAL-c340t-59ae67aca7c9f6a42f291e31ea34a31c96d2ce161a5c37383235bf77c275cd583</cites><orcidid>0000-0001-8601-1226</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,777,781,882,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38218680$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://inserm.hal.science/inserm-04395125$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Mathiot, Laurent</creatorcontrib><creatorcontrib>Nigen, Benoit</creatorcontrib><creatorcontrib>Goronflot, Thomas</creatorcontrib><creatorcontrib>Hiret, Sandrine</creatorcontrib><creatorcontrib>Doucet, Ludovic</creatorcontrib><creatorcontrib>Pons-Tostivint, Elvire</creatorcontrib><creatorcontrib>Bennouna, Jaafar</creatorcontrib><creatorcontrib>Denis, Marc G</creatorcontrib><creatorcontrib>Herbreteau, Guillaume</creatorcontrib><creatorcontrib>Raimbourg, Judith</creatorcontrib><title>Prognostic Impact of TP53 Mutations in Metastatic Nonsquamous Non-small-cell Lung Cancer</title><title>Clinical lung cancer</title><addtitle>Clin Lung Cancer</addtitle><description>The prognostic impact of TP53 mutations in advanced or metastatic nonsquamous non-small-cell lung cancer (nsNSCLC) patients treated with chemotherapy and/or immune checkpoint inhibitors (ICI) remains unclear.
We retrospectively collected data from patients with nsNSCLC treated in the first line from January 2018 to May 2021. The patient was separated into 2 groups according to their TP53 mutation status (wt vs. mut). Survival was estimated through the Kaplan-Meier method and compared by log-rank test.
Of 220 patients included, 126 were in the mutTP53 group, and 94 were in the wtTP53wt group. Median OS (mOS) was not significantly different between the mutTP53 and wtTP53 groups [17.5 months (95% confidence interval (CI), 11.3-21.5) vs. 9.5 months (95% CI, 7.4-14.2), (P = .051)]. In subgroup analyses, the mutTP53 group treated with ICI had a significantly improved mOS compared to the wtTP53 group [(24.7 months (95% CI, 20.8-not reach) vs. 12.0 months (95% CI, 4.7-not reach), (P = .017)] and mPFS [(9.6 months (95% CI, 5.8-not reach) vs. 3.2 months (95% CI, 1.3-13.8) (P = .048)]. There was no difference in terms of mOS and mPFS between the mutTP53 and the wtTP53 group treated by chemotherapy alone or combined with ICI.
TP53 mutation had no survival impact in the overall population, but is associated with better outcomes with ICI alone. These results suggest that patients with TP53 mutations could be treated with ICI alone, and wild-type patients could benefit from the addition of chemotherapy.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Carcinoma, Non-Small-Cell Lung - drug therapy</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - mortality</subject><subject>Carcinoma, Non-Small-Cell Lung - pathology</subject><subject>Female</subject><subject>Humans</subject><subject>Immune Checkpoint Inhibitors - therapeutic use</subject><subject>Life Sciences</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - mortality</subject><subject>Lung Neoplasms - pathology</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Prognosis</subject><subject>Retrospective Studies</subject><subject>Survival Rate</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><issn>1525-7304</issn><issn>1938-0690</issn><issn>1938-0690</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9UctOwzAQtBCI8voBDshHDiTYu7ETH1EFtFJ5HIrEzVpcB1Ll0cYJEn9PohZOO7uaGe3uMHYpRSyF1Lfr2JWli0EAxhJiIZIDdiINZpHQRhwOWIGKUhTJhJ2GsBYCNEo4ZhPMQGY6Eyfs_bVtPusmdIXj82pDruNNzpevCvlT31FXNHXgRc2ffEdh7B1_HkbbnqqmDyOOQkVlGTlflnzR1598SrXz7Tk7yqkM_mJfz9jbw_1yOosWL4_z6d0icpiILlKGvE7JUepMrimBHIz0KD1hQiid0StwXmpJymGKGQKqjzxNHaTKrVSGZ-xm5_tFpd20RUXtj22osLO7hS3q4NvKigSNkqC-5UC_3tE3bbPtfehsVYRxd6r9cJAFA0YgYjZSYUd1bRNC6_N_eynsGIBd2zEAOwZgJdghgEF0tffvPyq_-pf8fRx_AQvBgUk</recordid><startdate>20240501</startdate><enddate>20240501</enddate><creator>Mathiot, Laurent</creator><creator>Nigen, Benoit</creator><creator>Goronflot, Thomas</creator><creator>Hiret, Sandrine</creator><creator>Doucet, Ludovic</creator><creator>Pons-Tostivint, Elvire</creator><creator>Bennouna, Jaafar</creator><creator>Denis, Marc G</creator><creator>Herbreteau, Guillaume</creator><creator>Raimbourg, Judith</creator><general>Elsevier</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0001-8601-1226</orcidid></search><sort><creationdate>20240501</creationdate><title>Prognostic Impact of TP53 Mutations in Metastatic Nonsquamous Non-small-cell Lung Cancer</title><author>Mathiot, Laurent ; Nigen, Benoit ; Goronflot, Thomas ; Hiret, Sandrine ; Doucet, Ludovic ; Pons-Tostivint, Elvire ; Bennouna, Jaafar ; Denis, Marc G ; Herbreteau, Guillaume ; Raimbourg, Judith</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c340t-59ae67aca7c9f6a42f291e31ea34a31c96d2ce161a5c37383235bf77c275cd583</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Carcinoma, Non-Small-Cell Lung - drug therapy</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - mortality</topic><topic>Carcinoma, Non-Small-Cell Lung - pathology</topic><topic>Female</topic><topic>Humans</topic><topic>Immune Checkpoint Inhibitors - therapeutic use</topic><topic>Life Sciences</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - mortality</topic><topic>Lung Neoplasms - pathology</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Prognosis</topic><topic>Retrospective Studies</topic><topic>Survival Rate</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mathiot, Laurent</creatorcontrib><creatorcontrib>Nigen, Benoit</creatorcontrib><creatorcontrib>Goronflot, Thomas</creatorcontrib><creatorcontrib>Hiret, Sandrine</creatorcontrib><creatorcontrib>Doucet, Ludovic</creatorcontrib><creatorcontrib>Pons-Tostivint, Elvire</creatorcontrib><creatorcontrib>Bennouna, Jaafar</creatorcontrib><creatorcontrib>Denis, Marc G</creatorcontrib><creatorcontrib>Herbreteau, Guillaume</creatorcontrib><creatorcontrib>Raimbourg, Judith</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Clinical lung cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mathiot, Laurent</au><au>Nigen, Benoit</au><au>Goronflot, Thomas</au><au>Hiret, Sandrine</au><au>Doucet, Ludovic</au><au>Pons-Tostivint, Elvire</au><au>Bennouna, Jaafar</au><au>Denis, Marc G</au><au>Herbreteau, Guillaume</au><au>Raimbourg, Judith</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prognostic Impact of TP53 Mutations in Metastatic Nonsquamous Non-small-cell Lung Cancer</atitle><jtitle>Clinical lung cancer</jtitle><addtitle>Clin Lung Cancer</addtitle><date>2024-05-01</date><risdate>2024</risdate><volume>25</volume><issue>3</issue><spage>244</spage><epage>253.e2</epage><pages>244-253.e2</pages><issn>1525-7304</issn><issn>1938-0690</issn><eissn>1938-0690</eissn><abstract>The prognostic impact of TP53 mutations in advanced or metastatic nonsquamous non-small-cell lung cancer (nsNSCLC) patients treated with chemotherapy and/or immune checkpoint inhibitors (ICI) remains unclear.
We retrospectively collected data from patients with nsNSCLC treated in the first line from January 2018 to May 2021. The patient was separated into 2 groups according to their TP53 mutation status (wt vs. mut). Survival was estimated through the Kaplan-Meier method and compared by log-rank test.
Of 220 patients included, 126 were in the mutTP53 group, and 94 were in the wtTP53wt group. Median OS (mOS) was not significantly different between the mutTP53 and wtTP53 groups [17.5 months (95% confidence interval (CI), 11.3-21.5) vs. 9.5 months (95% CI, 7.4-14.2), (P = .051)]. In subgroup analyses, the mutTP53 group treated with ICI had a significantly improved mOS compared to the wtTP53 group [(24.7 months (95% CI, 20.8-not reach) vs. 12.0 months (95% CI, 4.7-not reach), (P = .017)] and mPFS [(9.6 months (95% CI, 5.8-not reach) vs. 3.2 months (95% CI, 1.3-13.8) (P = .048)]. There was no difference in terms of mOS and mPFS between the mutTP53 and the wtTP53 group treated by chemotherapy alone or combined with ICI.
TP53 mutation had no survival impact in the overall population, but is associated with better outcomes with ICI alone. These results suggest that patients with TP53 mutations could be treated with ICI alone, and wild-type patients could benefit from the addition of chemotherapy.</abstract><cop>United States</cop><pub>Elsevier</pub><pmid>38218680</pmid><doi>10.1016/j.cllc.2023.12.004</doi><orcidid>https://orcid.org/0000-0001-8601-1226</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Antineoplastic Combined Chemotherapy Protocols - therapeutic use Carcinoma, Non-Small-Cell Lung - drug therapy Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - mortality Carcinoma, Non-Small-Cell Lung - pathology Female Humans Immune Checkpoint Inhibitors - therapeutic use Life Sciences Lung Neoplasms - drug therapy Lung Neoplasms - genetics Lung Neoplasms - mortality Lung Neoplasms - pathology Male Middle Aged Mutation Prognosis Retrospective Studies Survival Rate Tumor Suppressor Protein p53 - genetics |
| title | Prognostic Impact of TP53 Mutations in Metastatic Nonsquamous Non-small-cell Lung Cancer |
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