{"title":"阿法替尼与化疗治疗伴有罕见表皮生长因子受体突变的非小细胞肺癌患者的实用随机研究：ACHILLES/TORG1834。","authors":"Satoru Miura, Hiroshi Tanaka, Toshihiro Misumi, Hiroshige Yoshioka, Takaaki Tokito, Tatsuro Fukuhara, Yuki Sato, Yoshimasa Shiraishi, Katsuhiko Naoki, Hiroaki Akamatsu, Ou Yamaguchi, Toshihide Yokoyama, Shoichi Kuyama, Kazumi Nishino, Naoki Furuya, Takayasu Kurata, Terufumi Kato, Satoshi Ikeda, Hidehito Horinouchi, Eiki Ichihara, Masahide Mori, Yuichi Takiguchi, Kentaro Tanaka, Yasuhiro Goto, Hiroaki Okamoto","doi":"10.1200/JCO-24-02007","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>To our knowledge, the ACHILLES/TORG1834 trial is the first randomized study comparing afatinib and chemotherapy in patients with non-small cell lung cancer (NSCLC) harboring sensitizing uncommon epidermal growth factor receptor (<i>EGFR</i>) mutations.</p><p><strong>Methods: </strong>This randomized, open-label study was performed at 51 Japanese institutions and recruited treatment-naïve patients with nonsquamous NSCLC with uncommon <i>EGFR</i> mutations, excluding exon 20 insertions and T790M mutations. Patients were randomly assigned 2:1 to receive afatinib (30 or 40 mg orally, at the treating physician's discretion) or a combination of platinum (cisplatin or carboplatin) and pemetrexed, followed by pemetrexed maintenance. The primary end point was progression-free survival (PFS). Secondary end points included objective response rate (ORR), overall survival, and safety. A prespecified interim analysis was planned to provide clinically meaningful information promptly, along with a crossover recommendation if necessary.</p><p><strong>Results: </strong>A total of 109 patients were enrolled between March 2019 and February 2023. In the interim analysis, the Data and Safety Monitoring Committee recommended early study termination. The median PFS was significantly longer in patients receiving afatinib than in those undergoing chemotherapy (10.6 <i>v</i> 5.7 months; hazard ratio, 0.421 [95% CI, 0.251 to 0.706]; <i>P</i> = .0010). ORRs to afatinib were similar across the overall population and among participants with major uncommon (G719X, L861Q, and S768I), compound, and other mutations (61.7%, 55.8%, 72.7%, and 60.0%, respectively). The most common grade 3 or higher adverse events were diarrhea, paronychia, and rash for afatinib, and appetite loss and nausea for chemotherapy.</p><p><strong>Conclusion: </strong>Afatinib should be considered the standard initial therapy for patients with NSCLC with sensitizing uncommon <i>EGFR</i> mutations.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2402007"},"PeriodicalIF":42.1000,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Pragmatic Randomized Study of Afatinib Versus Chemotherapy for Patients With Non-Small Cell Lung Cancer With Uncommon Epidermal Growth Factor Receptor Mutations: ACHILLES/TORG1834.\",\"authors\":\"Satoru Miura, Hiroshi Tanaka, Toshihiro Misumi, Hiroshige Yoshioka, Takaaki Tokito, Tatsuro Fukuhara, Yuki Sato, Yoshimasa Shiraishi, Katsuhiko Naoki, Hiroaki Akamatsu, Ou Yamaguchi, Toshihide Yokoyama, Shoichi Kuyama, Kazumi Nishino, Naoki Furuya, Takayasu Kurata, Terufumi Kato, Satoshi Ikeda, Hidehito Horinouchi, Eiki Ichihara, Masahide Mori, Yuichi Takiguchi, Kentaro Tanaka, Yasuhiro Goto, Hiroaki Okamoto\",\"doi\":\"10.1200/JCO-24-02007\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>To our knowledge, the ACHILLES/TORG1834 trial is the first randomized study comparing afatinib and chemotherapy in patients with non-small cell lung cancer (NSCLC) harboring sensitizing uncommon epidermal growth factor receptor (<i>EGFR</i>) mutations.</p><p><strong>Methods: </strong>This randomized, open-label study was performed at 51 Japanese institutions and recruited treatment-naïve patients with nonsquamous NSCLC with uncommon <i>EGFR</i> mutations, excluding exon 20 insertions and T790M mutations. Patients were randomly assigned 2:1 to receive afatinib (30 or 40 mg orally, at the treating physician's discretion) or a combination of platinum (cisplatin or carboplatin) and pemetrexed, followed by pemetrexed maintenance. The primary end point was progression-free survival (PFS). Secondary end points included objective response rate (ORR), overall survival, and safety. A prespecified interim analysis was planned to provide clinically meaningful information promptly, along with a crossover recommendation if necessary.</p><p><strong>Results: </strong>A total of 109 patients were enrolled between March 2019 and February 2023. In the interim analysis, the Data and Safety Monitoring Committee recommended early study termination. The median PFS was significantly longer in patients receiving afatinib than in those undergoing chemotherapy (10.6 <i>v</i> 5.7 months; hazard ratio, 0.421 [95% CI, 0.251 to 0.706]; <i>P</i> = .0010). ORRs to afatinib were similar across the overall population and among participants with major uncommon (G719X, L861Q, and S768I), compound, and other mutations (61.7%, 55.8%, 72.7%, and 60.0%, respectively). The most common grade 3 or higher adverse events were diarrhea, paronychia, and rash for afatinib, and appetite loss and nausea for chemotherapy.</p><p><strong>Conclusion: </strong>Afatinib should be considered the standard initial therapy for patients with NSCLC with sensitizing uncommon <i>EGFR</i> mutations.</p>\",\"PeriodicalId\":15384,\"journal\":{\"name\":\"Journal of Clinical Oncology\",\"volume\":\" \",\"pages\":\"JCO2402007\"},\"PeriodicalIF\":42.1000,\"publicationDate\":\"2025-04-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1200/JCO-24-02007\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1200/JCO-24-02007","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Pragmatic Randomized Study of Afatinib Versus Chemotherapy for Patients With Non-Small Cell Lung Cancer With Uncommon Epidermal Growth Factor Receptor Mutations: ACHILLES/TORG1834.
Purpose: To our knowledge, the ACHILLES/TORG1834 trial is the first randomized study comparing afatinib and chemotherapy in patients with non-small cell lung cancer (NSCLC) harboring sensitizing uncommon epidermal growth factor receptor (EGFR) mutations.
Methods: This randomized, open-label study was performed at 51 Japanese institutions and recruited treatment-naïve patients with nonsquamous NSCLC with uncommon EGFR mutations, excluding exon 20 insertions and T790M mutations. Patients were randomly assigned 2:1 to receive afatinib (30 or 40 mg orally, at the treating physician's discretion) or a combination of platinum (cisplatin or carboplatin) and pemetrexed, followed by pemetrexed maintenance. The primary end point was progression-free survival (PFS). Secondary end points included objective response rate (ORR), overall survival, and safety. A prespecified interim analysis was planned to provide clinically meaningful information promptly, along with a crossover recommendation if necessary.
Results: A total of 109 patients were enrolled between March 2019 and February 2023. In the interim analysis, the Data and Safety Monitoring Committee recommended early study termination. The median PFS was significantly longer in patients receiving afatinib than in those undergoing chemotherapy (10.6 v 5.7 months; hazard ratio, 0.421 [95% CI, 0.251 to 0.706]; P = .0010). ORRs to afatinib were similar across the overall population and among participants with major uncommon (G719X, L861Q, and S768I), compound, and other mutations (61.7%, 55.8%, 72.7%, and 60.0%, respectively). The most common grade 3 or higher adverse events were diarrhea, paronychia, and rash for afatinib, and appetite loss and nausea for chemotherapy.
Conclusion: Afatinib should be considered the standard initial therapy for patients with NSCLC with sensitizing uncommon EGFR mutations.
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The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.
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