Real‐World Study of EGFR‐TKI Rechallenge With Another TKI After First‐Line Osimertinib Discontinuation in Patients With EGFR‐Mutated Non‐Small Cell Lung Cancer: A Subset Analysis of the Reiwa Study
ABSTRACT Introduction First‐line osimertinib is widely used to treat patients with epidermal growth factor receptor (EGFR)‐mutated non‐small cell lung cancers (NSCLC). In clinical practice, rechallenge therapy with another EGFR‐tyrosine kinase inhibitor (TKI) is often performed after first‐line TKI...
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| Format: | Article |
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Wiley
2025-01-01
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| Series: | Thoracic Cancer |
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| Online Access: | https://doi.org/10.1111/1759-7714.15507 |
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| author | Kei Sonehara Kazunari Tateishi Kiyotaka Yoh Kazuhiro Usui Yukio Hosomi Kazuma Kishi Go Naka Kageaki Watanabe Shu Tamano Kohei Uemura Hideo Kunitoh |
| author_facet | Kei Sonehara Kazunari Tateishi Kiyotaka Yoh Kazuhiro Usui Yukio Hosomi Kazuma Kishi Go Naka Kageaki Watanabe Shu Tamano Kohei Uemura Hideo Kunitoh |
| author_sort | Kei Sonehara |
| collection | DOAJ |
| description | ABSTRACT Introduction First‐line osimertinib is widely used to treat patients with epidermal growth factor receptor (EGFR)‐mutated non‐small cell lung cancers (NSCLC). In clinical practice, rechallenge therapy with another EGFR‐tyrosine kinase inhibitor (TKI) is often performed after first‐line TKI discontinuation owing to resistance or toxicity; however, the efficacy and toxicity of EGFR‐TKI rechallenge after first‐line osimertinib have not been adequately investigated. This study aimed to examine the efficacy and safety of EGFR‐TKI rechallenge with another TKI. Methods This multicenter prospective observational study enrolled patients with EGFR‐mutated NSCLC who received first‐line osimertinib and another EGFR‐TKI as second‐ or third‐line treatment between September 2018 and August 2020. Results Fifty‐three patients received rechallenge with another EGFR‐TKI in the second‐line (n = 38, 71.7%) or third‐line (n = 15, 28.3%) setting. The primary reason for first‐line osimertinib discontinuation was toxicity in 32 (60.4%, 17 patients with pneumonitis) and disease progression in 20 (37.7%) patients. The most common rechallenge EGFR‐TKI was afatinib (n = 24, 45.3%), followed by gefitinib (n = 16, 30.2%) and erlotinib (n = 8, 15.1%). The real‐world time to treatment failure (rwTTF) was 7.3 months. The rwTTF for the toxicity discontinuation and progressive disease discontinuation groups was 9.3 months and 5.1 months, respectively, (HR 1.61, p = 0.119). EGFR‐TKI rechallenge was discontinued due to toxicity in nine patients (17.0%), but no patient developed pneumonitis. Conclusion EGFR‐TKI rechallenge with another TKI is well tolerated in patients with EGFR‐mutated NSCLC. Thus, it may be a useful treatment option after first‐line osimertinib failure, especially after osimertinib discontinuation due to toxicity. |
| format | Article |
| id | doaj-art-b1f6c4f29e5245aaa2131f26bdc0b4fd |
| institution | Kabale University |
| issn | 1759-7706 1759-7714 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Thoracic Cancer |
| spelling | doaj-art-b1f6c4f29e5245aaa2131f26bdc0b4fd2025-01-30T22:40:34ZengWileyThoracic Cancer1759-77061759-77142025-01-01162n/an/a10.1111/1759-7714.15507Real‐World Study of EGFR‐TKI Rechallenge With Another TKI After First‐Line Osimertinib Discontinuation in Patients With EGFR‐Mutated Non‐Small Cell Lung Cancer: A Subset Analysis of the Reiwa StudyKei Sonehara0Kazunari Tateishi1Kiyotaka Yoh2Kazuhiro Usui3Yukio Hosomi4Kazuma Kishi5Go Naka6Kageaki Watanabe7Shu Tamano8Kohei Uemura9Hideo Kunitoh10First Department of Internal Medicine Shinshu University School of Medicine Matsumoto JapanFirst Department of Internal Medicine Shinshu University School of Medicine Matsumoto JapanDepartment of Thoracic Oncology National Cancer Center Hospital East Chiba JapanRespiratory Medicine NTT Medical Center Tokyo Shinagawa Tokyo JapanDepartment of Thoracic Oncology and Respiratory Medicine Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Bunkyo Tokyo JapanDepartment of Respiratory Medicine Toho University Omori Medical Center Ota Tokyo JapanDepartment of Respiratory Medicine National Center for Global Health and Medicine Shinjuku Tokyo JapanDepartment of Thoracic Oncology and Respiratory Medicine Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Bunkyo Tokyo JapanBiostatistics and Bioinformatics Course, Graduate School of Interdisciplinary Information Studies The University of Tokyo Bunkyo Tokyo JapanDepartment of Biostatistics and Bioinformatics, the Interfaculty Initiative in Information Studies The University of Tokyo Bunkyo Tokyo JapanDepartment of Chemotherapy Japanese Red Cross Medical Center Shibuya Tokyo JapanABSTRACT Introduction First‐line osimertinib is widely used to treat patients with epidermal growth factor receptor (EGFR)‐mutated non‐small cell lung cancers (NSCLC). In clinical practice, rechallenge therapy with another EGFR‐tyrosine kinase inhibitor (TKI) is often performed after first‐line TKI discontinuation owing to resistance or toxicity; however, the efficacy and toxicity of EGFR‐TKI rechallenge after first‐line osimertinib have not been adequately investigated. This study aimed to examine the efficacy and safety of EGFR‐TKI rechallenge with another TKI. Methods This multicenter prospective observational study enrolled patients with EGFR‐mutated NSCLC who received first‐line osimertinib and another EGFR‐TKI as second‐ or third‐line treatment between September 2018 and August 2020. Results Fifty‐three patients received rechallenge with another EGFR‐TKI in the second‐line (n = 38, 71.7%) or third‐line (n = 15, 28.3%) setting. The primary reason for first‐line osimertinib discontinuation was toxicity in 32 (60.4%, 17 patients with pneumonitis) and disease progression in 20 (37.7%) patients. The most common rechallenge EGFR‐TKI was afatinib (n = 24, 45.3%), followed by gefitinib (n = 16, 30.2%) and erlotinib (n = 8, 15.1%). The real‐world time to treatment failure (rwTTF) was 7.3 months. The rwTTF for the toxicity discontinuation and progressive disease discontinuation groups was 9.3 months and 5.1 months, respectively, (HR 1.61, p = 0.119). EGFR‐TKI rechallenge was discontinued due to toxicity in nine patients (17.0%), but no patient developed pneumonitis. Conclusion EGFR‐TKI rechallenge with another TKI is well tolerated in patients with EGFR‐mutated NSCLC. Thus, it may be a useful treatment option after first‐line osimertinib failure, especially after osimertinib discontinuation due to toxicity.https://doi.org/10.1111/1759-7714.15507epidermal growth factor receptornon‐small cell lung cancerosimertinibrechallengetyrosine kinase inhibitor |
| spellingShingle | Kei Sonehara Kazunari Tateishi Kiyotaka Yoh Kazuhiro Usui Yukio Hosomi Kazuma Kishi Go Naka Kageaki Watanabe Shu Tamano Kohei Uemura Hideo Kunitoh Real‐World Study of EGFR‐TKI Rechallenge With Another TKI After First‐Line Osimertinib Discontinuation in Patients With EGFR‐Mutated Non‐Small Cell Lung Cancer: A Subset Analysis of the Reiwa Study Thoracic Cancer epidermal growth factor receptor non‐small cell lung cancer osimertinib rechallenge tyrosine kinase inhibitor |
| title | Real‐World Study of EGFR‐TKI Rechallenge With Another TKI After First‐Line Osimertinib Discontinuation in Patients With EGFR‐Mutated Non‐Small Cell Lung Cancer: A Subset Analysis of the Reiwa Study |
| title_full | Real‐World Study of EGFR‐TKI Rechallenge With Another TKI After First‐Line Osimertinib Discontinuation in Patients With EGFR‐Mutated Non‐Small Cell Lung Cancer: A Subset Analysis of the Reiwa Study |
| title_fullStr | Real‐World Study of EGFR‐TKI Rechallenge With Another TKI After First‐Line Osimertinib Discontinuation in Patients With EGFR‐Mutated Non‐Small Cell Lung Cancer: A Subset Analysis of the Reiwa Study |
| title_full_unstemmed | Real‐World Study of EGFR‐TKI Rechallenge With Another TKI After First‐Line Osimertinib Discontinuation in Patients With EGFR‐Mutated Non‐Small Cell Lung Cancer: A Subset Analysis of the Reiwa Study |
| title_short | Real‐World Study of EGFR‐TKI Rechallenge With Another TKI After First‐Line Osimertinib Discontinuation in Patients With EGFR‐Mutated Non‐Small Cell Lung Cancer: A Subset Analysis of the Reiwa Study |
| title_sort | real world study of egfr tki rechallenge with another tki after first line osimertinib discontinuation in patients with egfr mutated non small cell lung cancer a subset analysis of the reiwa study |
| topic | epidermal growth factor receptor non‐small cell lung cancer osimertinib rechallenge tyrosine kinase inhibitor |
| url | https://doi.org/10.1111/1759-7714.15507 |
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