The relative importance of predictive factors for single first-generation EGFR-TKI use for more than 5 years in patients with advanced non-small cell lung cancer: Taiwan multicenter TIPS-5 study

Huang, Ying-Hsuan; Hung, Jen Yu; Ko, How Wen; Su, Po‐Lan; Lai, Ching‐Huang; Huang, Chang; Hsia, Te Chun; Lin, Sheng; Wu, Kwou-Yeung; Yang, Cheng‐Ta; Su, Wu Chou; Chu, Yi Chun; Wang, Chin Chou; Liao, Wan-Chun; Lin, Yen Ting; Lin, Chung‐Sheng; Lin, Meng C.; Hsu, Kuo-Hsuan; Tseng, Jeng‐Sen; Yang, Tsung Ying; Chen, Kun Chieh; Lee, Hsuan-Shu; Yu, Sung-Liang; Ho, Cheng-Maw; Chang, Gee Chen

doi:10.1177/17588359211018022

Cited by 4 publications

(2 citation statements)

References 36 publications

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“…[34][35][36] Older age, poor performance status, and CNS metastasis are known unfavorable clinical factors associated with survival and outcome in advanced EGFR-mutated patients. 37,38 Among the patients with unknown T790M status in our study, 62 patients still received osimertinib (n = 25) and other 3G EGFR-TKIs (n = 37). Chemotherapy is currently recommended as second-line therapy for EGFRmutated patients without secondary T790M after 1G/2G EGFR-TKI therapy because the genetic alterations in T790M-negative patients are heterogeneous and resistant to osimertinib or other 3G EGFR-TKIs.…”

Section: Discussionmentioning

confidence: 94%

Sequential treatment in advanced non–small cell lung cancer harboring EGFR mutations

Hsu

Chang

et al. 2022

Ther Adv Respir Dis

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Background: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are standard treatments for advanced EGFR-mutated non–small cell lung cancer (NSCLC) patients. Osimertinib is an effective therapy for NSCLC patients with acquired resistance due to T790M mutation after first- and second-generation EGFR-TKI treatment. This study aimed to analyze the clinical outcomes of sequential therapy following first-line EGFR-TKIs and the predictive factors of an acquired T790M mutation. Methods: Between January 2014 and December 2018, data from 2190 advanced NSCLC patients with common EGFR mutations (exon 19 deletion and L858R) receiving first- and second-generation EGFR-TKIs in Linkou, Kaohsiung, Chiayi and Keelung Chang Gung Memorial Hospitals were retrospectively retrieved and analyzed. Results: Until August 2021, among 1943 patients who experienced progressive disease, 526 underwent T790M mutation tests, and their T790M-positive rate was 53.6%. Exon 19 deletion mutation and progression-free survival (PFS) of >12 months were positively associated with secondary T790M mutation. Different first-line first- and second-generation EGFR-TKI therapies did not affect the appearance of acquired T790M mutations. The median overall survival (OS) was 58.3 [95% confidence interval (CI): 49.0–67.5] months among the patients with T790M mutation who received second-line osimertinib therapy compared with 31.0 (95% CI: 27.5–34.5) months among the patients without T790M mutation who received chemotherapy alone. The multivariate analysis showed that a poor performance status (score: >2), nonadenocarcinoma histology, stage IV cancer, liver metastasis, brain metastasis, PFS while on first-line EGFR-TKIs, and subsequent chemotherapy without third-generation EGFR-TKIs were significant independent unfavorable prognostic factors for OS. Conclusion: This study demonstrated the efficacy of first-line EGFR-TKIs and sequential osimertinib therapy. The results of our study suggest that T790M mutation tests are important for the use of subsequent osimertinib, which yielded favorable survival outcomes.

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Section: Discussionmentioning

confidence: 94%

Sequential treatment in advanced non–small cell lung cancer harboring EGFR mutations

Hsu

Chang

et al. 2022

Ther Adv Respir Dis

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“…Previous studies have shown that patients with EGFR-mutated NSCLC with baseline liver and brain metastases had shorter PFS after EGFR-TKI therapy and unfavorable outcomes [ 15 , 24 , 26 – 28 ]. Our study identified that patients with liver metastasis had shorter PFS than those without liver metastasis, which is consistent with findings in the study by Li et al [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Afatinib in Untreated Stage IIIB/IV Lung Adenocarcinoma with Major Uncommon Epidermal Growth Factor Receptor (EGFR) Mutations (G719X/L861Q/S768I): A Multicenter Observational Study in Taiwan

et al. 2023

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Background Real-world clinical experience with afatinib as a treatment for advanced lung adenocarcinoma harboring uncommon epidermal growth factor receptor (EGFR) mutations (G719X, L861Q and S768I) has rarely been reported. Objective We aimed to perform a retrospective multicenter study to analyze afatinib therapy in untreated advanced lung adenocarcinoma harboring uncommon EGFR mutations. Patients and Methods Between May 2014 and June 2021, the data of 90 stage IIIB/IV lung adenocarcinoma patients with uncommon EGFR mutations (G719X/L861Q/S768I) treated with first-line afatinib from the cancer center database of Linkou, Tucheng, and Kaohsiung Chang Gung Memorial Hospitals were retrospectively retrieved and analyzed. Results Afatinib had an objective response rate (ORR) of 63.3% and a disease control rate (DCR) of 86.7%. The median progression-free survival (PFS) with first-line afatinib therapy was 17.3 months (95% confidence interval (CI), 12.07-22.53), and the median overall survival (OS) was 28.5 months (95% CI,) in all study patients. In the multivariate analysis, poor performance (Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2) and brain and liver metastases were independent predictors of unfavorable PFS. The G719X mutation (alone+compound) was an independent predictor of favorable PFS (hazard ratio (HR) = 0.578; 95% CI, 0.355−0.941; P = 0.027). Most afatinib-related adverse events (AEs) were limited to grades 1 and 2 and were manageable.

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Concomitant genomic features stratify prognosis to patients with advanced EGFR mutant lung cancer

Liang,

Xu,

Jiang

et al. 2024

Molecular Carcinogenesis

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This study aimed to explore the clinical significance of genomics features including tumor mutation burden (TMB) and copy number alteration (CNA) for advanced EGFR mutant lung cancer. We retrospectively identified 1378 patients with advanced EGFR mutant lung cancer and next‐generation sequencing tests from three cohorts. Multiple co‐occurring genomics alternations occurred in a large proportion (97%) of patients with advanced EGFR mutant lung cancers. Both TMB and CNA were predictive biomarkers for these patients. A joint analysis of TMB and CNA found that patients with high TMB and high CNA showed worse responses to EGFR‐TKIs and predicted worse outcomes. TMBhighCNAhigh, as a high‐risk genomic feature, showed predictive ability in most of the subgroups based on clinical characteristics. These patients had larger numbers of metastatic sites, and higher rates of EGFR copy number amplification, TP53 mutations, and cell‐cycle gene alterations, which showed more potential survival gain from combination treatment. Furthermore, a nomogram based on genomic features and clinical features was developed to distinguish prognosis. Genomic features could stratify prognosis and guide clinical treatment for patients with advanced EGFR mutant lung cancer.

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The relative importance of predictive factors for single first-generation EGFR-TKI use for more than 5 years in patients with advanced non-small cell lung cancer: Taiwan multicenter TIPS-5 study

Cited by 4 publications

References 36 publications

Sequential treatment in advanced non–small cell lung cancer harboring EGFR mutations

Sequential treatment in advanced non–small cell lung cancer harboring EGFR mutations

Afatinib in Untreated Stage IIIB/IV Lung Adenocarcinoma with Major Uncommon Epidermal Growth Factor Receptor (EGFR) Mutations (G719X/L861Q/S768I): A Multicenter Observational Study in Taiwan

Concomitant genomic features stratify prognosis to patients with advanced EGFR mutant lung cancer

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