Cancer Research and Treatment

Original Articles

Lung and Thoracic cancer

The Clinical Outcomes of Different First-Line EGFR-TKIs Plus Bevacizumab in Advanced EGFR-Mutant Lung Adenocarcinoma: Yen-Hsiang Huang, Kuo-Hsuan Hsu, Chun-Shih Chin, Jeng-Sen Tseng, Tsung-Ying Yang, Kun-Chieh Chen, Kang-Yi Su, Sung-Liang Yu, Jeremy J.W. Chen, Gee-Chen Chang; Cancer Res Treat. 2022;54(2):434-444. Published online August 2, 2021; DOI: https://doi.org/10.4143/crt.2021.671

Purpose
The aim of this study was to investigate the efficacy of various epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) plus bevacizumab in advanced EGFR-mutant lung adenocarcinoma patients.
Materials and Methods
From August 2016 to October 2020, we enrolled advanced lung adenocarcinoma patients harboring exon 19 deletion or L858R receiving gefitinib, erlotinib and afatinib plus bevacizumab as the first-line treatment for the purposes of analysis.
Results
A total of 36 patients were included in the final analysis. Three patients received gefitinib, 17 received erlotinib, and 16 received afatinib combined with bevacizumab as the first-line treatment. The objective response rate was 77.8%, and disease control rate was 94.4%. The overall median progression-free survival (PFS) was 16.4 months, while the median PFS was 17.1 months in patients with exon 19 deletion, and 16.2 months in patients with L858R mutation (p=0.311). Regarding the use of different EGFR-TKIs, the median PFS was 17.1 months in the erlotinib group and 21.6 months in the afatinib group (p=0.617). In patients with brain metastasis at baseline, the median PFS was 18.9 months in the erlotinib group and 16.4 months in the afatinib group (p=0.747). Amongst patients harboring exon 19 deletion, the median PFS was 16.2 months in the erlotinib group and not-reached in the afatinib group (p=0.141). In patients with L858R mutation, the median PFS was 18.9 months in the erlotinib group and 16.2 months in the afatinib group (p=0.481).
Conclusion
Our research demonstrates that not only erlotinib combined with bevacizumab, but also afatinib plus bevacizumab as first-line treatment, provides solid clinical efficacy in advanced EGFR-mutant lung adenocarcinoma patients.

Citations

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Clinical outcome of bevacizumab or ramucirumab combined with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors as the first line therapy in susceptible EGFR‐mutated advanced non‐small‐cell lung
Chia‐Yu Kuo, Ming‐Ju Tsai, Jen‐Yu Hung, Mei‐Hsuan Lee, Kuan‐Li Wu, Yu‐Chen Tsai, Cheng‐Hao Chuang, Chung‐Wen Huang, Chin‐Ling Chen, Chih‐Jen Yang, Inn‐Wen Chong
The Kaohsiung Journal of Medical Sciences.2024; 40(5): 467. CrossRef
Scorpiones, Scolopendra and Gekko Inhibit Lung Cancer Growth and Metastasis by Ameliorating Hypoxic Tumor Microenvironment via PI3K/AKT/mTOR/HIF-1α Signaling Pathway
Qi-yuan Mao, Xue-qian Wang, Fei Lin, Ming-wei Yu, Hui-ting Fan, Qi Zheng, Lan-chun Liu, Chu-chu Zhang, Dao-rui Li, Hong-sheng Lin
Chinese Journal of Integrative Medicine.2024; 30(9): 799. CrossRef
Real-world clinical efficacy of bevacizumab biosimilar in patients with advanced non-small-cell lung cancer
Wei-Fan Ou, Kuo-Hsuan Hsu, Jeng-Sen Tseng, Po-Hsin Lee, Kun-Chieh Chen, Yen-Hsiang Huang, Gee-Chen Chang, Tsung-Ying Yang
Therapeutic Advances in Medical Oncology.2024;[Epub] CrossRef
Bevacizumab plus erlotinib versus erlotinib alone for advanced EGFR-mutant non-small cell lung cancer: a meta-analysis of randomized clinical trials
Ruijian Li, Weiyi Li, Fang Zhang, Shanshan Li
European Journal of Medical Research.2023;[Epub] CrossRef
Bevacizumab versus Ramucirumab in EGFR-Mutated Metastatic Non-Small-Cell Lung Cancer Patients: A Real-World Observational Study
Wen-Chien Cheng, Yi-Cheng Shen, Chieh-Lung Chen, Wei-Chih Liao, Chia-Hung Chen, Hung-Jen Chen, Chih-Yen Tu, Te-Chun Hsia
Cancers.2023; 15(3): 642. CrossRef
Afatinib/bevacizumab/erlotinib

Reactions Weekly.2023; 1952(1): 32. CrossRef
Comprehensive analysis of prediction of the EGFR mutation and subtypes based on the spinal metastasis from primary lung adenocarcinoma
Ran Cao, Huanhuan Chen, Huan Wang, Yan Wang, E-Nuo Cui, Wenyan Jiang
Frontiers in Oncology.2023;[Epub] CrossRef
When to add anti-angiogenesis drugs to EGFR-mutated metastatic non–small cell lung cancer patients: a real-world study from Taiwan
Chieh-Lung Chen, Sing-Ting Wang, Wei-Chih Liao, Chia-Hung Chen, Chih-Yen Tu, Hung-Jen Chen, Te-Chun Hsia, Wen-Chien Cheng
BMC Cancer.2022;[Epub] CrossRef
State-of-the-Art Molecular Oncology of Lung Cancer in Taiwan
Yung-Hung Luo, Kung-Hao Liang, Hsu-Ching Huang, Chia-I Shen, Chi-Lu Chiang, Mong-Lien Wang, Shih-Hwa Chiou, Yuh-Min Chen
International Journal of Molecular Sciences.2022; 23(13): 7037. CrossRef
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
Suey-Haur Lee, Yu-Ching Lin, Li-Chung Chiu, Jia-Shiuan Ju, Pi-Hung Tung, Allen Chung-Cheng Huang, Shih-Hong Li, Yueh-Fu Fang, Chih-Hung Chen, Scott Chih-Hsi Kuo, Chin-Chou Wang, Cheng-Ta Yang, Ping-Chih Hsu
Therapeutic Advances in Medical Oncology.2022;[Epub] CrossRef
The efficacy and tolerability of combining pemetrexed-based chemotherapy with gefitinib in the first-line treatment of non-small cell lung cancer with mutated EGFR: A pooled analysis of randomized clinical trials
Bi-Cheng Wang, Wen-Xuan Zhang, Bo-Hua Kuang, Guo-He Lin, Alessandro Rizzo
PLOS ONE.2022; 17(10): e0275919. CrossRef

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The Association of Acquired T790M Mutation with Clinical Characteristics after Resistance to First-Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in Lung Adenocarcinoma: Yen-Hsiang Huang, Kuo-Hsuan Hsu, Jeng-Sen Tseng, Kun-Chieh Chen, Chia-Hung Hsu, Kang-Yi Su, Jeremy J. W. Chen, Huei-Wen Chen, Sung-Liang Yu, Tsung-Ying Yang, Gee-Chen Chang; Cancer Res Treat. 2018;50(4):1294-1303. Published online January 4, 2018; DOI: https://doi.org/10.4143/crt.2017.512

Abstract PDF Supplementary Material PubReader ePub

Purpose
The main objective of this study was to investigate the relationship among the clinical characteristics and the frequency of T790M mutation in advanced epidermal growth factor receptor (EGFR)‒mutant lung adenocarcinoma patients with acquired resistance after firstline EGFR‒tyrosine kinase inhibitor (TKI) treatment.
Materials and Methods
We enrolled EGFR-mutant stage IIIB-IV lung adenocarcinoma patients, who had progressed to prior EGFR-TKI therapy, and evaluated their rebiopsy EGFR mutation status.
Results
A total of 205 patients were enrolled for analysis. The overall T790M mutation rate of rebiopsy was 46.3%. The T790M mutation rates among patients with exon 19 deletion mutation, exon 21 L858R point mutation, and other mutations were 55.0%, 37.3%, and 27.3%, respectively. Baseline exon 19 deletion was associated with a significantly higher frequency of T790M mutation (adjusted odds ratio, 2.14; 95% confidence interval [CI], 1.20 to 3.83; p=0.010). In the exon 19 deletion subgroup, there was a greater prevalence of T790M mutation than other exon 19 deletion subtypes in patients with the Del E746-A750 mutation (61.6% vs. 40.6%; odds ratio, 2.35; 95% CI, 1.01 to 5.49; p=0.049). The progression-free survival (PFS) of first-line TKI treatment > 11 months was also associated with a higher T790M mutation rate (54.1% vs. 39.3%; adjusted odds ratio, 1.82; 95% CI, 1.02 to 3.25; p=0.044). Patients who underwent rebiopsy at metastatic sites had more chance to harbor T790M mutation (52.6% vs. 33.8%; adjusted odds ratio, 1.97; 95% CI, 1.06 to 3.67; p=0.032).
Conclusion
PFS of first-line EGFR-TKI, rebiopsy site, EGFR exon 19 deletion and its subtype Del E746- A750 mutation are associated with the frequency of T790M mutation.

Citations

Citations to this article as recorded by

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Kazumi Nishino, Jin-Yuan Shih, Kazuhiko Nakagawa, Martin Reck, Edward B. Garon, Michelle Carlsen, Tomoko Matsui, Carla Visseren-Grul, Ernest Nadal
JTO Clinical and Research Reports.2024; 5(2): 100624. CrossRef
Epidermal Growth Factor Receptor Exon 19 Deletion Subtypes Do Not Influence Survival Outcomes Following First-line Epidermal Growth Factor Receptor-tyrosine Kinase Inhibitors in Advanced Nonsmall Cell Lung Cancer Patients
Yan-Jei Tang, John Wen-Cheng Chang, Chen-Yang Huang, Yueh-Fu Fang, Ching-Fu Chang, Cheng-Ta Yang, Chih-Hsi Scott Kuo, Ping-Chih Hsu, Chiao-En Wu
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Thoracic Cancer.2023; 14(4): 363. CrossRef
Monitoring of T790M in plasma ctDNA of advanced EGFR-mutant NSCLC patients on first- or second-generation tyrosine kinase inhibitors
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The Clinical Outcomes of Different First-Line EGFR-TKIs Plus Bevacizumab in Advanced EGFR-Mutant Lung Adenocarcinoma
Yen-Hsiang Huang, Kuo-Hsuan Hsu, Chun-Shih Chin, Jeng-Sen Tseng, Tsung-Ying Yang, Kun-Chieh Chen, Kang-Yi Su, Sung-Liang Yu, Jeremy J.W. Chen, Gee-Chen Chang
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Impact of EGFR exon 19 deletion subtypes on clinical outcomes in EGFR-TKI-Treated advanced non-small-cell lung cancer
Le-Tian Huang, Shu-Ling Zhang, Cheng-Bo Han, Jie-Tao Ma
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Risk Stratification Using a Novel Nomogram for 2190 EGFR-Mutant NSCLC Patients Receiving the First or Second Generation EGFR-TKI
John Wen-Cheng Chang, Chen-Yang Huang, Yueh-Fu Fang, Ching-Fu Chang, Cheng-Ta Yang, Chih-Hsi Scott Kuo, Ping-Chih Hsu, Chiao-En Wu
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Rong Liu, Jianying Zhou, Xia Ling
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Yung-Hung Luo, Kung-Hao Liang, Hsu-Ching Huang, Chia-I Shen, Chi-Lu Chiang, Mong-Lien Wang, Shih-Hwa Chiou, Yuh-Min Chen
International Journal of Molecular Sciences.2022; 23(13): 7037. CrossRef
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Prior EGFR-TKI Treatment in EGFR-Mutated NSCLC Affects the Allele Frequency Fraction of Acquired T790M and the Subsequent Efficacy of Osimertinib
Chih-Hsi Scott Kuo, Chi-Hsien Huang, Chien-Ying Liu, Stelios Pavlidis, Ho-Wen Ko, Fu-Tsai Chung, Tin-Yu Lin, Chih-Liang Wang, Yi-Ke Guo, Cheng-Ta Yang
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Intercalated Treatment Following Rebiopsy Is Associated with a Shorter Progression-Free Survival of Osimertinib Treatment: Jeng-Sen Tseng, Tsung-Ying Yang, Kun-Chieh Chen, Kuo-Hsuan Hsu, Yen-Hsiang Huang, Kang-Yi Su, Sung-Liang Yu, Gee-Chen Chang; Cancer Res Treat. 2018;50(4):1164-1174. Published online December 11, 2017; DOI: https://doi.org/10.4143/crt.2017.460

Abstract PDF Supplementary Material PubReader ePub

Purpose
Epidermal growth factor receptor (EGFR) T790M mutation serves as an important predictor of osimertinib efficacy. However, little is known about how it works among patients with various timings of T790M emergence and treatment.
Materials and Methods
Advanced EGFR-mutant lung adenocarcinoma patients with positive T790M mutation in tumor were retrospectively enrolled and observed to determine the outcomes of osimertinib treatment. We evaluated the association between patients’ characteristics and the efficacy of osimertinib treatment, particularly with respect to the timing of T790M emergence and osimertinib prescription.
Results
A total of 91 patients were enrolled, including 14 (15.4%) with primary and 77 (84.6%) with acquired T790M mutation. The objective response rate and disease controlratewere 60.9% and 85.1%, respectively. The median progression-free survival (PFS) and overall survival were 11.5 months (95% confidence interval [CI], 9.0 to 14.0) and 30.4 months (95% CI, 11.3 to 49.5), respectively. There was no significant difference in response rate and PFS between primary and acquired T790M populations. In the acquired T790M subgroup, patientswho received osimertinib after T790M had been confirmed by rebiopsy had a longer PFS than those with intercalated treatments between rebiopsy and osimertinib prescription (14.0 months [95% CI, 9.0 to 18.9] vs. 7.2 months [95% CI, 3.7 to 10.8]; adjusted hazard ratio, 0.48 [95% CI, 0.24 to 0.98; p=0.043]). Rebiopsy timing did not influence the outcome.
Conclusion
Osimertinib prescription with intercalated treatment following rebiopsy but not the timing of T790M emergence influenced the treatment outcome. We suggest that it is better to start osimertinib treatment once T790M mutation has been confirmed by biopsy.

Citations

Citations to this article as recorded by

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Post-Progression Survival in Secondary EGFR T790M-Mutated Non-Small-Cell Lung Cancer Patients With and Without Osimertinib After Failure of a Previous EGFR TKI
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Targeted Oncology.2020; 15(4): 503. CrossRef
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Targeted Oncology.2019; 14(4): 433. CrossRef

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