PMID- 36424878 OWN - NLM STAT- MEDLINE DCOM- 20230104 LR - 20231213 IS - 1759-7714 (Electronic) IS - 1759-7706 (Print) IS - 1759-7706 (Linking) VI - 14 IP - 1 DP - 2023 Jan TI - Epidermal growth factor receptor tyrosine kinase inhibitors for non-small cell lung cancer harboring uncommon EGFR mutations: Real-world data from Taiwan. PG - 12-23 LID - 10.1111/1759-7714.14537 [doi] AB - BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the standard treatment for patients with non-small cell lung cancer (NSCLC) harboring EGFR mutations. This study aimed to evaluate the efficacy of EGFR-TKIs and prognostic factors for patients with NSCLC harboring uncommon EGFR mutations, which account for 10% of EGFR mutations. METHODS: A total of 230 treatment-naive patients with NSCLC harboring uncommon EGFR mutations treated with first-line EGFR-TKIs between 2011 and 2018 at four hospitals (belonging to four institutions, Linkou, Kaohsiung, Keelung, and Chiayi, of the Chang Gung Memorial Hospital) in Taiwan were retrospectively reviewed. Their clinicopathological characteristics, adverse events (AEs), objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were collected. Univariate and multivariate analyses were performed to identify potential prognostic factors for PFS. RESULTS: Overall, patients who received afatinib (n = 62) had better PFS (median: 6.4 vs. 5.9 months, p = 0.022) and OS (median: 13.4 vs. 13.0 months, p = 0.008) than those who received gefitinib/erlotinib (n = 124), although no significant differences were observed for ORR (46.8% vs. 35.5%, p = 0.137) or DCR (59.7% vs. 58.9%, p = 0.916). Patients who received afatinib showed significantly higher ORR (58.3% vs. 31.3%, p = 0.027) but not DCR compared with gefitinib/erlotinib for major uncommon mutations. Afatinib trended toward better PFS and OS for major uncommon mutations and compound mutations. No EGFR-TKIs were effective for most NSCLC patients with exon 20 insertions. Performance status, metastasis of the liver and pleura, and dose reduction were independent prognostic factors for PFS. CONCLUSION: Afatinib demonstrated better survival outcomes than gefitinib/erlotinib for NSCLC patients harboring major EGFR uncommon mutations and compound mutations. Performance status and metastatic sites may be useful for predicting PFS for major uncommon mutations and compound mutations. CI - (c) 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd. FAU - Chang, John Wen-Cheng AU - Chang JW AD - Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan. FAU - Huang, Chen-Yang AU - Huang CY AD - Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan. FAU - Fang, Yueh-Fu AU - Fang YF AD - Division of Thoracic Oncology, Department of Thoracic Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan. FAU - Chang, Ching-Fu AU - Chang CF AD - Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan. FAU - Yang, Cheng-Ta AU - Yang CT AD - Division of Thoracic Oncology, Department of Thoracic Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan. FAU - Kuo, Chih-Hsi Scott AU - Kuo CS AD - Division of Thoracic Oncology, Department of Thoracic Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan. FAU - Hsu, Ping-Chih AU - Hsu PC AD - Division of Thoracic Oncology, Department of Thoracic Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan. FAU - Wu, Chiao-En AU - Wu CE AUID- ORCID: 0000-0002-1900-2984 AD - Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221124 PL - Singapore TA - Thorac Cancer JT - Thoracic cancer JID - 101531441 RN - 41UD74L59M (Afatinib) RN - S65743JHBS (Gefitinib) RN - DA87705X9K (Erlotinib Hydrochloride) RN - 0 (Tyrosine Kinase Inhibitors) RN - 0 (Protein Kinase Inhibitors) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.10.1 (EGFR protein, human) SB - IM MH - Humans MH - *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics/pathology MH - Afatinib/therapeutic use MH - Gefitinib/therapeutic use MH - Erlotinib Hydrochloride/therapeutic use/pharmacology MH - Tyrosine Kinase Inhibitors MH - *Lung Neoplasms/drug therapy/genetics/pathology MH - Retrospective Studies MH - Taiwan MH - Protein Kinase Inhibitors/therapeutic use/pharmacology MH - ErbB Receptors MH - Mutation PMC - PMC9807449 OTO - NOTNLM OT - afatinib OT - erlotinib OT - gefitinib OT - lung cancer OT - uncommon mutation COIS- The authors declare that there is no conflict of interest. EDAT- 2022/11/26 06:00 MHDA- 2023/01/05 06:00 PMCR- 2022/11/24 CRDT- 2022/11/25 02:04 PHST- 2022/05/23 00:00 [revised] PHST- 2022/03/28 00:00 [received] PHST- 2022/05/25 00:00 [accepted] PHST- 2022/11/26 06:00 [pubmed] PHST- 2023/01/05 06:00 [medline] PHST- 2022/11/25 02:04 [entrez] PHST- 2022/11/24 00:00 [pmc-release] AID - TCA14537 [pii] AID - 10.1111/1759-7714.14537 [doi] PST - ppublish SO - Thorac Cancer. 2023 Jan;14(1):12-23. doi: 10.1111/1759-7714.14537. Epub 2022 Nov 24.