Juwhan Choi, Jae Cheol Lee, In Ae Kim, Kye Young Lee, Jeong Eun Lee, Seung Hun Jang, Seong Hoon Yoon, In-Jae Oh, Sang Hoon Lee, Eun Young Kim, Sung Yong Lee
{"title":"第一代表皮生长因子受体酪氨酸激酶抑制剂在无T790M患者再治疗中的疗效和安全性。","authors":"Juwhan Choi, Jae Cheol Lee, In Ae Kim, Kye Young Lee, Jeong Eun Lee, Seung Hun Jang, Seong Hoon Yoon, In-Jae Oh, Sang Hoon Lee, Eun Young Kim, Sung Yong Lee","doi":"10.21037/tlcr-2025-36","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Patients receiving first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) and undergoing second and/or third-line cytotoxic chemotherapy may experience regrowth of EGFR (+) clones. Retreatment with EGFR TKIs can provide antitumor effects and potentially induce T790M-positive conversion. This study evaluated the efficacy, safety, and T790M (+) conversion rates in patients without T790M mutation at the second biopsy retreated with first-generation EGFR TKIs as third-line or subsequent therapy.</p><p><strong>Methods: </strong>This open-label, multi-center, prospective phase II trial (NCT03382795) enrolled patients with non-small cell lung cancer (NSCLC) previously treated with first- or second-generation EGFR TKIs and cytotoxic chemotherapy They were retreated with gefitinib or erlotinib. Key endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety.</p><p><strong>Results: </strong>Among 63 patients (34 on gefitinib, 29 on erlotinib), ORR was 14.3%. Median PFS was 2.2 months, and median OS was 8.6 months. Adverse events occurred in 82.5% of patients, primarily grade ≤2. The T790M conversion rate was 31.7% and was significantly associated with prior EGFR TKI exposure duration (P=0.047). Patients with T790M conversion had a median OS of 29.3 months, significantly (P<0.001) longer than the median OS of 6.0 months for non-converters. Next-generation sequencing (NGS) of pre-retreatment blood samples identified additional T790M mutations (20.8%) undetected by conventional testing. Low TP53 expression showed a non-significant trend toward higher tendency T790M conversion (66.7% <i>vs.</i> 30.8%, P=0.32).</p><p><strong>Conclusions: </strong>EGFR retreatment induced T790M conversion in 32% of cases, enabling third-generation EGFR TKIs, leading to a substantial improvement in median OS. Blood-based NGS identified additional T790M mutations, undetected by routine polymerase chain reaction (PCR). EGFR TKI retreatment with blood-based NGS may enhance patient prognosis by identifying additional T790M positive mutations.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2483-2493"},"PeriodicalIF":3.5000,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337059/pdf/","citationCount":"0","resultStr":"{\"title\":\"Efficacy and safety of first-generation epidermal growth factor receptor tyrosine kinase inhibitors in retreatment of patients without T790M.\",\"authors\":\"Juwhan Choi, Jae Cheol Lee, In Ae Kim, Kye Young Lee, Jeong Eun Lee, Seung Hun Jang, Seong Hoon Yoon, In-Jae Oh, Sang Hoon Lee, Eun Young Kim, Sung Yong Lee\",\"doi\":\"10.21037/tlcr-2025-36\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Patients receiving first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) and undergoing second and/or third-line cytotoxic chemotherapy may experience regrowth of EGFR (+) clones. Retreatment with EGFR TKIs can provide antitumor effects and potentially induce T790M-positive conversion. This study evaluated the efficacy, safety, and T790M (+) conversion rates in patients without T790M mutation at the second biopsy retreated with first-generation EGFR TKIs as third-line or subsequent therapy.</p><p><strong>Methods: </strong>This open-label, multi-center, prospective phase II trial (NCT03382795) enrolled patients with non-small cell lung cancer (NSCLC) previously treated with first- or second-generation EGFR TKIs and cytotoxic chemotherapy They were retreated with gefitinib or erlotinib. Key endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety.</p><p><strong>Results: </strong>Among 63 patients (34 on gefitinib, 29 on erlotinib), ORR was 14.3%. Median PFS was 2.2 months, and median OS was 8.6 months. Adverse events occurred in 82.5% of patients, primarily grade ≤2. The T790M conversion rate was 31.7% and was significantly associated with prior EGFR TKI exposure duration (P=0.047). Patients with T790M conversion had a median OS of 29.3 months, significantly (P<0.001) longer than the median OS of 6.0 months for non-converters. Next-generation sequencing (NGS) of pre-retreatment blood samples identified additional T790M mutations (20.8%) undetected by conventional testing. Low TP53 expression showed a non-significant trend toward higher tendency T790M conversion (66.7% <i>vs.</i> 30.8%, P=0.32).</p><p><strong>Conclusions: </strong>EGFR retreatment induced T790M conversion in 32% of cases, enabling third-generation EGFR TKIs, leading to a substantial improvement in median OS. Blood-based NGS identified additional T790M mutations, undetected by routine polymerase chain reaction (PCR). EGFR TKI retreatment with blood-based NGS may enhance patient prognosis by identifying additional T790M positive mutations.</p>\",\"PeriodicalId\":23271,\"journal\":{\"name\":\"Translational lung cancer research\",\"volume\":\"14 7\",\"pages\":\"2483-2493\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2025-07-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337059/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Translational lung cancer research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.21037/tlcr-2025-36\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/7/28 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational lung cancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/tlcr-2025-36","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/7/28 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Efficacy and safety of first-generation epidermal growth factor receptor tyrosine kinase inhibitors in retreatment of patients without T790M.
Background: Patients receiving first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) and undergoing second and/or third-line cytotoxic chemotherapy may experience regrowth of EGFR (+) clones. Retreatment with EGFR TKIs can provide antitumor effects and potentially induce T790M-positive conversion. This study evaluated the efficacy, safety, and T790M (+) conversion rates in patients without T790M mutation at the second biopsy retreated with first-generation EGFR TKIs as third-line or subsequent therapy.
Methods: This open-label, multi-center, prospective phase II trial (NCT03382795) enrolled patients with non-small cell lung cancer (NSCLC) previously treated with first- or second-generation EGFR TKIs and cytotoxic chemotherapy They were retreated with gefitinib or erlotinib. Key endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety.
Results: Among 63 patients (34 on gefitinib, 29 on erlotinib), ORR was 14.3%. Median PFS was 2.2 months, and median OS was 8.6 months. Adverse events occurred in 82.5% of patients, primarily grade ≤2. The T790M conversion rate was 31.7% and was significantly associated with prior EGFR TKI exposure duration (P=0.047). Patients with T790M conversion had a median OS of 29.3 months, significantly (P<0.001) longer than the median OS of 6.0 months for non-converters. Next-generation sequencing (NGS) of pre-retreatment blood samples identified additional T790M mutations (20.8%) undetected by conventional testing. Low TP53 expression showed a non-significant trend toward higher tendency T790M conversion (66.7% vs. 30.8%, P=0.32).
Conclusions: EGFR retreatment induced T790M conversion in 32% of cases, enabling third-generation EGFR TKIs, leading to a substantial improvement in median OS. Blood-based NGS identified additional T790M mutations, undetected by routine polymerase chain reaction (PCR). EGFR TKI retreatment with blood-based NGS may enhance patient prognosis by identifying additional T790M positive mutations.
期刊介绍：
Translational Lung Cancer Research(TLCR, Transl Lung Cancer Res, Print ISSN 2218-6751; Online ISSN 2226-4477) is an international, peer-reviewed, open-access journal, which was founded in March 2012. TLCR is indexed by PubMed/PubMed Central and the Chemical Abstracts Service (CAS) Databases. It is published quarterly the first year, and published bimonthly since February 2013. It provides practical up-to-date information on prevention, early detection, diagnosis, and treatment of lung cancer. Specific areas of its interest include, but not limited to, multimodality therapy, markers, imaging, tumor biology, pathology, chemoprevention, and technical advances related to lung cancer.
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