Prospective exosome-focused translational research for afatinib (EXTRA) study of patients with nonsmall cell lung cancer harboring EGFR mutation: an observational clinical study
Background: The exosome-focused translational research for afatinib (EXTRA) study is the first trial to identify novel predictive biomarkers for longer treatment efficacy of afatinib in patients with epidermal growth factor receptor (EGFR) mutation-positive nonsmall cell lung cancer (NSCLC) via a co...
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| Veröffentlicht in: | Therapeutic advances in medical oncology 2023-01, Vol.15, p.17588359231177021-17588359231177021 |
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| creator | Takata, Saori Morikawa, Kei Tanaka, Hisashi Itani, Hidetoshi Ishihara, Masashi Horiuchi, Kazuya Kato, Yasuhiro Ikemura, Shinnosuke Nakagawa, Hideyuki Nakahara, Yoshiro Seki, Yoshitaka Bessho, Akihiro Takahashi, Nobumasa Hayashi, Kentaro Endo, Takeo Takeyama, Kiyoshi Maekura, Toshiya Takigawa, Nagio Kawase, Akikazu Endoh, Makoto Nemoto, Kenji Kishi, Kazuma Soejima, Kenzo Okuma, Yusuke Yoshimura, Kenichi Saigusa, Daisuke Kanai, Yae Ueda, Koji Togashi, Akira Matsutani, Noriyuki Seki, Nobuhiko |
| description | Background:
The exosome-focused translational research for afatinib (EXTRA) study is the first trial to identify novel predictive biomarkers for longer treatment efficacy of afatinib in patients with epidermal growth factor receptor (EGFR) mutation-positive nonsmall cell lung cancer (NSCLC) via a comprehensive association study using genomic, proteomic, epigenomic, and metabolomic analyses.
Objectives:
We report details of the clinical portion prior to omics analyses.
Design:
A prospective, single-arm, observational study was conducted using afatinib 40 mg/day as an initial dose in untreated patients with EGFR mutation-positive NSCLC. Dose reduction to 20 mg every other day was allowed.
Methods:
Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated.
Results:
A total of 103 patients (median age 70 years, range 42–88 years) were enrolled from 21 institutions in Japan between February 2017 and March 2018. After a median follow-up of 35.0 months, 21% remained on afatinib treatment, whereas 9% had discontinued treatment because of AEs. The median PFS was 18.4 months, with a 3-year PFS rate of 23.3%. The median afatinib treatment duration in patients with final doses of 40 (n = 27), 30 (n = 23), and 20 mg/day (n = 35), and 20 mg every other day (n = 18) were 13.4, 15.4, 18.8, and 18.3 months, respectively. The median OS was not reached, with a 3-year OS rate of 58.5%. The median OS in patients who did (n = 25) and did not (n = 78) receive osimertinib during the entire course of treatment were 42.4 months and not reached, respectively (p = 0.654).
Conclusions:
As the largest prospective study in Japan, this study confirmed favorable OS following first-line afatinib in patients with EGFR mutation-positive NSCLC in a real-world setting. Further analysis of the EXTRA study is expected to identify novel predictive biomarkers for afatinib.
Trial registration:
UMIN-CTR identifier (UMIN000024935, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_his_list.cgi?recptno=R000028688 |
| doi_str_mv | 10.1177/17588359231177021 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10262622</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.1177_17588359231177021</sage_id><sourcerecordid>2827253022</sourcerecordid><originalsourceid>FETCH-LOGICAL-c467t-7eeca93b6884cb8f8bbab820b3959885e07192d27ac13ff572b24fa896133ed13</originalsourceid><addsrcrecordid>eNp1Uttu1DAQjRCIXuADeEGWeCkPKb4kscMLqqptQaoEqorEWzR2xrupEnuxk4V-Vv8QZ7ctBYQs2ePjM-d47MmyV4weMyblOyZLpURZczFvKWdPsv0Zy2fw6aN4LzuI8ZrSqioq-jzbE1KkHCX3s9svwcc1mrHbIMGfPvoBc-vNFLElYwAXexg776AnASNCMCtifSBgE-w6TY4W364uT96SOE7tDfGWrNMBujGSH924Is67OEDfE4Np6ie3JAacwUBWELQPXQIW52eXZJjGrdF7Ao54HTFs7o1Nn5xMCrYeL7JnFvqIL-_Ww-zr2eLq9GN-8fn80-nJRW6KSo65RDRQC10pVRitrNIatOJUi7qslSqRSlbzlkswTFhbSq55YUHVFRMCWyYOsw873fWkB2xNqilA36xDN0C4aTx0zZ8nrls1S79pGOVVGjwpHN0pBP99wjg2QxfndwCHfooNV1zyUtAt9c1f1Gs_hVR8YtWclkXNeZVYbMcy6dNiQPtwG0abuQWafzoi5bx-XMZDxn0LJMLxjhBhib9t_6_4Cyxgwm0</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2920549226</pqid></control><display><type>article</type><title>Prospective exosome-focused translational research for afatinib (EXTRA) study of patients with nonsmall cell lung cancer harboring EGFR mutation: an observational clinical study</title><source>DOAJ Directory of Open Access Journals</source><source>Sage Journals GOLD Open Access 2024</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Takata, Saori ; Morikawa, Kei ; Tanaka, Hisashi ; Itani, Hidetoshi ; Ishihara, Masashi ; Horiuchi, Kazuya ; Kato, Yasuhiro ; Ikemura, Shinnosuke ; Nakagawa, Hideyuki ; Nakahara, Yoshiro ; Seki, Yoshitaka ; Bessho, Akihiro ; Takahashi, Nobumasa ; Hayashi, Kentaro ; Endo, Takeo ; Takeyama, Kiyoshi ; Maekura, Toshiya ; Takigawa, Nagio ; Kawase, Akikazu ; Endoh, Makoto ; Nemoto, Kenji ; Kishi, Kazuma ; Soejima, Kenzo ; Okuma, Yusuke ; Yoshimura, Kenichi ; Saigusa, Daisuke ; Kanai, Yae ; Ueda, Koji ; Togashi, Akira ; Matsutani, Noriyuki ; Seki, Nobuhiko</creator><creatorcontrib>Takata, Saori ; Morikawa, Kei ; Tanaka, Hisashi ; Itani, Hidetoshi ; Ishihara, Masashi ; Horiuchi, Kazuya ; Kato, Yasuhiro ; Ikemura, Shinnosuke ; Nakagawa, Hideyuki ; Nakahara, Yoshiro ; Seki, Yoshitaka ; Bessho, Akihiro ; Takahashi, Nobumasa ; Hayashi, Kentaro ; Endo, Takeo ; Takeyama, Kiyoshi ; Maekura, Toshiya ; Takigawa, Nagio ; Kawase, Akikazu ; Endoh, Makoto ; Nemoto, Kenji ; Kishi, Kazuma ; Soejima, Kenzo ; Okuma, Yusuke ; Yoshimura, Kenichi ; Saigusa, Daisuke ; Kanai, Yae ; Ueda, Koji ; Togashi, Akira ; Matsutani, Noriyuki ; Seki, Nobuhiko</creatorcontrib><description>Background:
The exosome-focused translational research for afatinib (EXTRA) study is the first trial to identify novel predictive biomarkers for longer treatment efficacy of afatinib in patients with epidermal growth factor receptor (EGFR) mutation-positive nonsmall cell lung cancer (NSCLC) via a comprehensive association study using genomic, proteomic, epigenomic, and metabolomic analyses.
Objectives:
We report details of the clinical portion prior to omics analyses.
Design:
A prospective, single-arm, observational study was conducted using afatinib 40 mg/day as an initial dose in untreated patients with EGFR mutation-positive NSCLC. Dose reduction to 20 mg every other day was allowed.
Methods:
Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated.
Results:
A total of 103 patients (median age 70 years, range 42–88 years) were enrolled from 21 institutions in Japan between February 2017 and March 2018. After a median follow-up of 35.0 months, 21% remained on afatinib treatment, whereas 9% had discontinued treatment because of AEs. The median PFS was 18.4 months, with a 3-year PFS rate of 23.3%. The median afatinib treatment duration in patients with final doses of 40 (n = 27), 30 (n = 23), and 20 mg/day (n = 35), and 20 mg every other day (n = 18) were 13.4, 15.4, 18.8, and 18.3 months, respectively. The median OS was not reached, with a 3-year OS rate of 58.5%. The median OS in patients who did (n = 25) and did not (n = 78) receive osimertinib during the entire course of treatment were 42.4 months and not reached, respectively (p = 0.654).
Conclusions:
As the largest prospective study in Japan, this study confirmed favorable OS following first-line afatinib in patients with EGFR mutation-positive NSCLC in a real-world setting. Further analysis of the EXTRA study is expected to identify novel predictive biomarkers for afatinib.
Trial registration:
UMIN-CTR identifier (UMIN000024935, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_his_list.cgi?recptno=R000028688</description><identifier>ISSN: 1758-8359</identifier><identifier>ISSN: 1758-8340</identifier><identifier>EISSN: 1758-8359</identifier><identifier>DOI: 10.1177/17588359231177021</identifier><identifier>PMID: 37323187</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Biomarkers ; Epidermal growth factor receptors ; Lung cancer ; Metabolomics ; Mutation ; Non-small cell lung carcinoma ; Original Research ; Patients ; Proteomics ; Translation</subject><ispartof>Therapeutic advances in medical oncology, 2023-01, Vol.15, p.17588359231177021-17588359231177021</ispartof><rights>The Author(s), 2023</rights><rights>The Author(s), 2023.</rights><rights>The Author(s), 2023. This work is licensed under the Creative Commons Attribution – Non-Commercial License https://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s), 2023 2023 SAGE Publications Ltd unless otherwise noted. Manuscript content on this site is licensed under Creative Commons Licenses</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c467t-7eeca93b6884cb8f8bbab820b3959885e07192d27ac13ff572b24fa896133ed13</citedby><cites>FETCH-LOGICAL-c467t-7eeca93b6884cb8f8bbab820b3959885e07192d27ac13ff572b24fa896133ed13</cites><orcidid>0000-0002-3835-5128 ; 0000-0002-0745-5118 ; 0000-0002-0394-7377 ; 0000-0001-8585-1995</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10262622/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10262622/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,21966,27853,27924,27925,44945,45333,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37323187$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Takata, Saori</creatorcontrib><creatorcontrib>Morikawa, Kei</creatorcontrib><creatorcontrib>Tanaka, Hisashi</creatorcontrib><creatorcontrib>Itani, Hidetoshi</creatorcontrib><creatorcontrib>Ishihara, Masashi</creatorcontrib><creatorcontrib>Horiuchi, Kazuya</creatorcontrib><creatorcontrib>Kato, Yasuhiro</creatorcontrib><creatorcontrib>Ikemura, Shinnosuke</creatorcontrib><creatorcontrib>Nakagawa, Hideyuki</creatorcontrib><creatorcontrib>Nakahara, Yoshiro</creatorcontrib><creatorcontrib>Seki, Yoshitaka</creatorcontrib><creatorcontrib>Bessho, Akihiro</creatorcontrib><creatorcontrib>Takahashi, Nobumasa</creatorcontrib><creatorcontrib>Hayashi, Kentaro</creatorcontrib><creatorcontrib>Endo, Takeo</creatorcontrib><creatorcontrib>Takeyama, Kiyoshi</creatorcontrib><creatorcontrib>Maekura, Toshiya</creatorcontrib><creatorcontrib>Takigawa, Nagio</creatorcontrib><creatorcontrib>Kawase, Akikazu</creatorcontrib><creatorcontrib>Endoh, Makoto</creatorcontrib><creatorcontrib>Nemoto, Kenji</creatorcontrib><creatorcontrib>Kishi, Kazuma</creatorcontrib><creatorcontrib>Soejima, Kenzo</creatorcontrib><creatorcontrib>Okuma, Yusuke</creatorcontrib><creatorcontrib>Yoshimura, Kenichi</creatorcontrib><creatorcontrib>Saigusa, Daisuke</creatorcontrib><creatorcontrib>Kanai, Yae</creatorcontrib><creatorcontrib>Ueda, Koji</creatorcontrib><creatorcontrib>Togashi, Akira</creatorcontrib><creatorcontrib>Matsutani, Noriyuki</creatorcontrib><creatorcontrib>Seki, Nobuhiko</creatorcontrib><title>Prospective exosome-focused translational research for afatinib (EXTRA) study of patients with nonsmall cell lung cancer harboring EGFR mutation: an observational clinical study</title><title>Therapeutic advances in medical oncology</title><addtitle>Ther Adv Med Oncol</addtitle><description>Background:
The exosome-focused translational research for afatinib (EXTRA) study is the first trial to identify novel predictive biomarkers for longer treatment efficacy of afatinib in patients with epidermal growth factor receptor (EGFR) mutation-positive nonsmall cell lung cancer (NSCLC) via a comprehensive association study using genomic, proteomic, epigenomic, and metabolomic analyses.
Objectives:
We report details of the clinical portion prior to omics analyses.
Design:
A prospective, single-arm, observational study was conducted using afatinib 40 mg/day as an initial dose in untreated patients with EGFR mutation-positive NSCLC. Dose reduction to 20 mg every other day was allowed.
Methods:
Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated.
Results:
A total of 103 patients (median age 70 years, range 42–88 years) were enrolled from 21 institutions in Japan between February 2017 and March 2018. After a median follow-up of 35.0 months, 21% remained on afatinib treatment, whereas 9% had discontinued treatment because of AEs. The median PFS was 18.4 months, with a 3-year PFS rate of 23.3%. The median afatinib treatment duration in patients with final doses of 40 (n = 27), 30 (n = 23), and 20 mg/day (n = 35), and 20 mg every other day (n = 18) were 13.4, 15.4, 18.8, and 18.3 months, respectively. The median OS was not reached, with a 3-year OS rate of 58.5%. The median OS in patients who did (n = 25) and did not (n = 78) receive osimertinib during the entire course of treatment were 42.4 months and not reached, respectively (p = 0.654).
Conclusions:
As the largest prospective study in Japan, this study confirmed favorable OS following first-line afatinib in patients with EGFR mutation-positive NSCLC in a real-world setting. Further analysis of the EXTRA study is expected to identify novel predictive biomarkers for afatinib.
Trial registration:
UMIN-CTR identifier (UMIN000024935, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_his_list.cgi?recptno=R000028688</description><subject>Biomarkers</subject><subject>Epidermal growth factor receptors</subject><subject>Lung cancer</subject><subject>Metabolomics</subject><subject>Mutation</subject><subject>Non-small cell lung carcinoma</subject><subject>Original Research</subject><subject>Patients</subject><subject>Proteomics</subject><subject>Translation</subject><issn>1758-8359</issn><issn>1758-8340</issn><issn>1758-8359</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>AFRWT</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNp1Uttu1DAQjRCIXuADeEGWeCkPKb4kscMLqqptQaoEqorEWzR2xrupEnuxk4V-Vv8QZ7ctBYQs2ePjM-d47MmyV4weMyblOyZLpURZczFvKWdPsv0Zy2fw6aN4LzuI8ZrSqioq-jzbE1KkHCX3s9svwcc1mrHbIMGfPvoBc-vNFLElYwAXexg776AnASNCMCtifSBgE-w6TY4W364uT96SOE7tDfGWrNMBujGSH924Is67OEDfE4Np6ie3JAacwUBWELQPXQIW52eXZJjGrdF7Ao54HTFs7o1Nn5xMCrYeL7JnFvqIL-_Ww-zr2eLq9GN-8fn80-nJRW6KSo65RDRQC10pVRitrNIatOJUi7qslSqRSlbzlkswTFhbSq55YUHVFRMCWyYOsw873fWkB2xNqilA36xDN0C4aTx0zZ8nrls1S79pGOVVGjwpHN0pBP99wjg2QxfndwCHfooNV1zyUtAt9c1f1Gs_hVR8YtWclkXNeZVYbMcy6dNiQPtwG0abuQWafzoi5bx-XMZDxn0LJMLxjhBhib9t_6_4Cyxgwm0</recordid><startdate>20230101</startdate><enddate>20230101</enddate><creator>Takata, Saori</creator><creator>Morikawa, Kei</creator><creator>Tanaka, Hisashi</creator><creator>Itani, Hidetoshi</creator><creator>Ishihara, Masashi</creator><creator>Horiuchi, Kazuya</creator><creator>Kato, Yasuhiro</creator><creator>Ikemura, Shinnosuke</creator><creator>Nakagawa, Hideyuki</creator><creator>Nakahara, Yoshiro</creator><creator>Seki, Yoshitaka</creator><creator>Bessho, Akihiro</creator><creator>Takahashi, Nobumasa</creator><creator>Hayashi, Kentaro</creator><creator>Endo, Takeo</creator><creator>Takeyama, Kiyoshi</creator><creator>Maekura, Toshiya</creator><creator>Takigawa, Nagio</creator><creator>Kawase, Akikazu</creator><creator>Endoh, Makoto</creator><creator>Nemoto, Kenji</creator><creator>Kishi, Kazuma</creator><creator>Soejima, Kenzo</creator><creator>Okuma, Yusuke</creator><creator>Yoshimura, Kenichi</creator><creator>Saigusa, Daisuke</creator><creator>Kanai, Yae</creator><creator>Ueda, Koji</creator><creator>Togashi, Akira</creator><creator>Matsutani, Noriyuki</creator><creator>Seki, Nobuhiko</creator><general>SAGE Publications</general><general>Sage Publications Ltd</general><scope>AFRWT</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3835-5128</orcidid><orcidid>https://orcid.org/0000-0002-0745-5118</orcidid><orcidid>https://orcid.org/0000-0002-0394-7377</orcidid><orcidid>https://orcid.org/0000-0001-8585-1995</orcidid></search><sort><creationdate>20230101</creationdate><title>Prospective exosome-focused translational research for afatinib (EXTRA) study of patients with nonsmall cell lung cancer harboring EGFR mutation: an observational clinical study</title><author>Takata, Saori ; Morikawa, Kei ; Tanaka, Hisashi ; Itani, Hidetoshi ; Ishihara, Masashi ; Horiuchi, Kazuya ; Kato, Yasuhiro ; Ikemura, Shinnosuke ; Nakagawa, Hideyuki ; Nakahara, Yoshiro ; Seki, Yoshitaka ; Bessho, Akihiro ; Takahashi, Nobumasa ; Hayashi, Kentaro ; Endo, Takeo ; Takeyama, Kiyoshi ; Maekura, Toshiya ; Takigawa, Nagio ; Kawase, Akikazu ; Endoh, Makoto ; Nemoto, Kenji ; Kishi, Kazuma ; Soejima, Kenzo ; Okuma, Yusuke ; Yoshimura, Kenichi ; Saigusa, Daisuke ; Kanai, Yae ; Ueda, Koji ; Togashi, Akira ; Matsutani, Noriyuki ; Seki, Nobuhiko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c467t-7eeca93b6884cb8f8bbab820b3959885e07192d27ac13ff572b24fa896133ed13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Biomarkers</topic><topic>Epidermal growth factor receptors</topic><topic>Lung cancer</topic><topic>Metabolomics</topic><topic>Mutation</topic><topic>Non-small cell lung carcinoma</topic><topic>Original Research</topic><topic>Patients</topic><topic>Proteomics</topic><topic>Translation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Takata, Saori</creatorcontrib><creatorcontrib>Morikawa, Kei</creatorcontrib><creatorcontrib>Tanaka, Hisashi</creatorcontrib><creatorcontrib>Itani, Hidetoshi</creatorcontrib><creatorcontrib>Ishihara, Masashi</creatorcontrib><creatorcontrib>Horiuchi, Kazuya</creatorcontrib><creatorcontrib>Kato, Yasuhiro</creatorcontrib><creatorcontrib>Ikemura, Shinnosuke</creatorcontrib><creatorcontrib>Nakagawa, Hideyuki</creatorcontrib><creatorcontrib>Nakahara, Yoshiro</creatorcontrib><creatorcontrib>Seki, Yoshitaka</creatorcontrib><creatorcontrib>Bessho, Akihiro</creatorcontrib><creatorcontrib>Takahashi, Nobumasa</creatorcontrib><creatorcontrib>Hayashi, Kentaro</creatorcontrib><creatorcontrib>Endo, Takeo</creatorcontrib><creatorcontrib>Takeyama, Kiyoshi</creatorcontrib><creatorcontrib>Maekura, Toshiya</creatorcontrib><creatorcontrib>Takigawa, Nagio</creatorcontrib><creatorcontrib>Kawase, Akikazu</creatorcontrib><creatorcontrib>Endoh, Makoto</creatorcontrib><creatorcontrib>Nemoto, Kenji</creatorcontrib><creatorcontrib>Kishi, Kazuma</creatorcontrib><creatorcontrib>Soejima, Kenzo</creatorcontrib><creatorcontrib>Okuma, Yusuke</creatorcontrib><creatorcontrib>Yoshimura, Kenichi</creatorcontrib><creatorcontrib>Saigusa, Daisuke</creatorcontrib><creatorcontrib>Kanai, Yae</creatorcontrib><creatorcontrib>Ueda, Koji</creatorcontrib><creatorcontrib>Togashi, Akira</creatorcontrib><creatorcontrib>Matsutani, Noriyuki</creatorcontrib><creatorcontrib>Seki, Nobuhiko</creatorcontrib><collection>Sage Journals GOLD Open Access 2024</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Therapeutic advances in medical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Takata, Saori</au><au>Morikawa, Kei</au><au>Tanaka, Hisashi</au><au>Itani, Hidetoshi</au><au>Ishihara, Masashi</au><au>Horiuchi, Kazuya</au><au>Kato, Yasuhiro</au><au>Ikemura, Shinnosuke</au><au>Nakagawa, Hideyuki</au><au>Nakahara, Yoshiro</au><au>Seki, Yoshitaka</au><au>Bessho, Akihiro</au><au>Takahashi, Nobumasa</au><au>Hayashi, Kentaro</au><au>Endo, Takeo</au><au>Takeyama, Kiyoshi</au><au>Maekura, Toshiya</au><au>Takigawa, Nagio</au><au>Kawase, Akikazu</au><au>Endoh, Makoto</au><au>Nemoto, Kenji</au><au>Kishi, Kazuma</au><au>Soejima, Kenzo</au><au>Okuma, Yusuke</au><au>Yoshimura, Kenichi</au><au>Saigusa, Daisuke</au><au>Kanai, Yae</au><au>Ueda, Koji</au><au>Togashi, Akira</au><au>Matsutani, Noriyuki</au><au>Seki, Nobuhiko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prospective exosome-focused translational research for afatinib (EXTRA) study of patients with nonsmall cell lung cancer harboring EGFR mutation: an observational clinical study</atitle><jtitle>Therapeutic advances in medical oncology</jtitle><addtitle>Ther Adv Med Oncol</addtitle><date>2023-01-01</date><risdate>2023</risdate><volume>15</volume><spage>17588359231177021</spage><epage>17588359231177021</epage><pages>17588359231177021-17588359231177021</pages><issn>1758-8359</issn><issn>1758-8340</issn><eissn>1758-8359</eissn><abstract>Background:
The exosome-focused translational research for afatinib (EXTRA) study is the first trial to identify novel predictive biomarkers for longer treatment efficacy of afatinib in patients with epidermal growth factor receptor (EGFR) mutation-positive nonsmall cell lung cancer (NSCLC) via a comprehensive association study using genomic, proteomic, epigenomic, and metabolomic analyses.
Objectives:
We report details of the clinical portion prior to omics analyses.
Design:
A prospective, single-arm, observational study was conducted using afatinib 40 mg/day as an initial dose in untreated patients with EGFR mutation-positive NSCLC. Dose reduction to 20 mg every other day was allowed.
Methods:
Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated.
Results:
A total of 103 patients (median age 70 years, range 42–88 years) were enrolled from 21 institutions in Japan between February 2017 and March 2018. After a median follow-up of 35.0 months, 21% remained on afatinib treatment, whereas 9% had discontinued treatment because of AEs. The median PFS was 18.4 months, with a 3-year PFS rate of 23.3%. The median afatinib treatment duration in patients with final doses of 40 (n = 27), 30 (n = 23), and 20 mg/day (n = 35), and 20 mg every other day (n = 18) were 13.4, 15.4, 18.8, and 18.3 months, respectively. The median OS was not reached, with a 3-year OS rate of 58.5%. The median OS in patients who did (n = 25) and did not (n = 78) receive osimertinib during the entire course of treatment were 42.4 months and not reached, respectively (p = 0.654).
Conclusions:
As the largest prospective study in Japan, this study confirmed favorable OS following first-line afatinib in patients with EGFR mutation-positive NSCLC in a real-world setting. Further analysis of the EXTRA study is expected to identify novel predictive biomarkers for afatinib.
Trial registration:
UMIN-CTR identifier (UMIN000024935, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_his_list.cgi?recptno=R000028688</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>37323187</pmid><doi>10.1177/17588359231177021</doi><orcidid>https://orcid.org/0000-0002-3835-5128</orcidid><orcidid>https://orcid.org/0000-0002-0745-5118</orcidid><orcidid>https://orcid.org/0000-0002-0394-7377</orcidid><orcidid>https://orcid.org/0000-0001-8585-1995</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1758-8359 |
| ispartof | Therapeutic advances in medical oncology, 2023-01, Vol.15, p.17588359231177021-17588359231177021 |
| issn | 1758-8359 1758-8340 1758-8359 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10262622 |
| source | DOAJ Directory of Open Access Journals; Sage Journals GOLD Open Access 2024; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Biomarkers Epidermal growth factor receptors Lung cancer Metabolomics Mutation Non-small cell lung carcinoma Original Research Patients Proteomics Translation |
| title | Prospective exosome-focused translational research for afatinib (EXTRA) study of patients with nonsmall cell lung cancer harboring EGFR mutation: an observational clinical study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T11%3A44%3A33IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Prospective%20exosome-focused%20translational%20research%20for%20afatinib%20(EXTRA)%20study%20of%20patients%20with%20nonsmall%20cell%20lung%20cancer%20harboring%20EGFR%20mutation:%20an%20observational%20clinical%20study&rft.jtitle=Therapeutic%20advances%20in%20medical%20oncology&rft.au=Takata,%20Saori&rft.date=2023-01-01&rft.volume=15&rft.spage=17588359231177021&rft.epage=17588359231177021&rft.pages=17588359231177021-17588359231177021&rft.issn=1758-8359&rft.eissn=1758-8359&rft_id=info:doi/10.1177/17588359231177021&rft_dat=%3Cproquest_pubme%3E2827253022%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2920549226&rft_id=info:pmid/37323187&rft_sage_id=10.1177_17588359231177021&rfr_iscdi=true |