First- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors in a large, real-world cohort of patients with non-small cell lung cancer

Huang, Allen Chung-Cheng; Huang, Chi-Hsien; Ju, Jia-Shiuan; Chiu, Tzu-Hsuan; Tung, Pi-Hung; Wang, Chin‐Chou; Liu, Chien-Ying; Chung, Fu‐Tsai; Fang, Yueh‐Fu; Guo, Yike; Kuo, Chih-Hsi S.; Yang, Cheng‐Ta

doi:10.1177/17588359211035710

Cited by 12 publications

(12 citation statements)

References 40 publications

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“…In the analysis of previous large cohort studies, the acquired EGFR-T790M mutation rate was higher in NSCLC patients taking first-generation EGFR-TKIs (gefitinib and erlotinib) than in those taking the second-generation EGFR-TKI afatinib. 42 , 43 The secondary EGFR-T790M mutation rates in our study were similar to those in previous cohort studies, and our results indicated that the addition of bevacizumab to first- and second-generation EGFR-TKIs did not affect the frequency or the trend of acquired EGFR-T790M mutation after disease progression.…”

Section: Discussionsupporting

confidence: 89%

Comparison of afatinib and erlotinib combined with bevacizumab in untreated stage IIIB/IV epidermal growth factor receptor-mutated lung adenocarcinoma patients: a multicenter clinical analysis study

et al. 2022

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Background: Although bevacizumab in combination with afatinib or erlotinib is an effective and safe first-line therapy for advanced epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC), there are very few clinical data comparing afatinib and erlotinib combined with bevacizumab. We performed a retrospective multicenter analysis for the comparison of two combination therapies. Methods: Between May 2015 and October 2020, data of 135 stage IIIB/IV EGFR-mutated NSCLC patients receiving first-line afatinib or erlotinib combined with bevacizumab combination therapy in Linkou, Keelung, Chiayi, and Kaohsiung Chang Gung Memorial Hospitals were retrieved and retrospectively analyzed. Results: In all, 67 patients received afatinib plus bevacizumab, and 68 patients received erlotinib plus bevacizumab. Afatinib combined with bevacizumab had an objective response rate (ORR) of 82.1% and a disease control rate (DCR) of 97.0%, and the ORR and DCR were 83.8 and 95.6%, respectively, in the erlotinib combined with bevacizumab group ( p = 0.798 and p = 1.000). The median progression-free survival was 20.7 and 20.3 months for the afatinib plus bevacizumab group and the erlotinib plus bevacizumab group, respectively [hazard ratio (HR) = 1.02; 95% confidence interval (CI), 0.891–1.953; p = 0.167). The overall survival was 41.9 and 51.0 months for the afatinib plus bevacizumab group and erlotinib plus bevacizumab group, respectively (HR = 1.42; 95% CI, 0.829–2.436; p = 0.201). The secondary EGFR-T790M mutation rates after disease progression were 44% in the afatinib plus bevacizumab group and 58.8% in the erlotinib plus bevacizumab group ( p = 0.165). Skin toxicity was the most frequent treatment-related adverse event (AE) in both treatment groups. Diarrhea, an AE, occurred significantly more frequently in the afatinib plus bevacizumab group than in the erlotinib plus bevacizumab group ( p < 0.05). Conclusion: Afatinib combined with bevacizumab was equally as effective as erlotinib combined with bevacizumab for untreated advanced EGFR-mutated NSCLC. Prospective clinical studies that explore bevacizumab combined with afatinib or erlotinib for advanced EGFR-mutated NSCLC are warranted.

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Section: Discussionsupporting

confidence: 89%

Comparison of afatinib and erlotinib combined with bevacizumab in untreated stage IIIB/IV epidermal growth factor receptor-mutated lung adenocarcinoma patients: a multicenter clinical analysis study

et al. 2022

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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: 98%

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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“…In Taiwan, 1G/2G EGFR-TKIs, gefitinib, erlotinib, and afatinib are all commonly prescribed as frontline therapy for EGFR-mutated NSCLC patients [ 22 , 23 ]. Although a previous study reported that frontline EGFR-TKIs (gefitinib, erlotinib, and afatinib) had a statistically significant difference in the T790M mutation rate (59.9%, 45.5%, and 52.7%, respectively; p = 0.037) [ 24 ], there was no significant difference in the T790M mutation rate after frontline treatment with different EGFR-TKIs.…”

Section: Discussionmentioning

confidence: 99%

Impact of T790M Mutation Status on Later-Line Osimertinib Treatment in Non-Small Cell Lung Cancer Patients

Tang

Chang

et al. 2022

Cancers

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Background: Osimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) designed to overcome acquired T790M resistance mutations in non-small cell lung cancer (NSCLC). However, the efficacy of osimertinib in patients without acquired T790M mutations has not been well studied. This study aimed to evaluate the efficacy of osimertinib in patients treated with first- and second-generation EGFR-TKIs followed by later-line osimertinib treatment. Patients: The clinical data and survival outcomes of 172 patients with advanced NSCLC treated with osimertinib following frontline EGFR-TKIs at Chang Gung Memorial Hospital from 2014 to 2018 were retrospectively reviewed. T790M mutations were detected using tissue sequencing and/or liquid biopsy. Results: A total of 172 EGFR-mutated NSCLC patients treated with frontline EGFR-TKI therapy followed by later-line osimertinib were enrolled in the current study and divided into three groups based on the T790M status (positive, negative, or unknown T790M). Patients with NSCLC harboring acquired T790M mutation treated with osimertinib had the best objective response rate (ORR) (52.6%, 25.0%, and 32.0%, p = 0.044), disease control rate (DCR) (79.3%, 41.7%, and 68.0%, p = 0.011), and progression-free survival (PFS, median PFS, 12.6, 3.1, 10.4 months, p = 0.001) among the three groups (positive, negative, and unknown T790M, respectively). However, a marked difference was found between positive and negative T790M mutations but not between positive and unknown T790M mutations. Univariate analysis was performed to identify potential prognostic factors for PFS in 172 patients treated with osimertinib. Lung metastasis (p < 0.001), brain metastasis (p < 0.009), number of metastatic sites (p < 0.001), PFS with frontline EGFR-TKIs (p = 0.03), and T790M status (p = 0.006) were identified as prognostic factors for PFS with osimertinib. Multivariate analysis showed that lung metastasis (p < 0.001) and PFS with frontline EGFR-TKIs and T790M status were independent prognostic factors. Conclusion: This study confirmed the greater efficacy of later-line osimertinib for NSCLC with acquired T790M mutation than for NSCLC without acquired T790M mutation. Detection of the T790M mutation after frontline treatment (first- and second-generation EGFR-TKI) is crucial for prolonging the survival of NSCLC patients harboring EGFR mutation. Osimertinib may be considered an option for NSCLC with unknown T790M mutations, as a certain subpopulation may benefit from osimertinib.

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First- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors in a large, real-world cohort of patients with non-small cell lung cancer

Cited by 12 publications

References 40 publications

Comparison of afatinib and erlotinib combined with bevacizumab in untreated stage IIIB/IV epidermal growth factor receptor-mutated lung adenocarcinoma patients: a multicenter clinical analysis study

Comparison of afatinib and erlotinib combined with bevacizumab in untreated stage IIIB/IV epidermal growth factor receptor-mutated lung adenocarcinoma patients: a multicenter clinical analysis study

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

Impact of T790M Mutation Status on Later-Line Osimertinib Treatment in Non-Small Cell Lung Cancer Patients

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