Cancer Research and Treatment

Original Articles

Lung and Thoracic cancer

Comparison of Clinicopathogenomic Features and Treatment Outcomes of EGFR and HER2 Exon 20 Insertion Mutations in Non–Small Cell Lung Cancer: Single-Institution Experience: So Heun Lee, Hyehyun Jeong, Deok Hoon Kim, Se Jin Jang, Sang-We Kim, Shinkyo Yoon, Dae Ho Lee; Cancer Res Treat. 2024;56(3):774-784. Published online January 30, 2024; DOI: https://doi.org/10.4143/crt.2023.1177

Abstract PDF PubReader ePub: Purpose
Exon 20 insertion mutations (E20ins) in epidermal growth factor receptor (EGFR) or human epidermal growth factor receptor 2 (HER2) in non–small cell lung cancer (NSCLC) patients has become more important with emergence of novel agents targeting E20ins.
Materials and Methods
Advanced/Metastatic NSCLC patients with E20ins were included. EGFR E20ins was identified by two methods, next-generation sequencing (NGS) or real-time polymerase chain reaction (PCR), while HER2 E20ins was done by NGS only.
Results
Between December 2013 and July 2021, E20ins were identified in 107 patients at Asan Medical Center; 67 EGFR E20ins and 40 HER2 E20ins. Out of 32 patients with EGFR E20ins who had tested both PCR and NGS, 17 were identified only through NGS and the other 15 through both tests, giving a discordance rate of 53.1%. There was no clinically significant difference in clinicopathologic features between EGFR and HER2 E20ins; both were observed more frequently in adenocarcinoma, female and never-smokers. Brain metastases were evident at diagnosis in 31.8% of EGFR E20ins and 27.5% of HER2 E20ins, respectively. Platinum-based doublets demonstrated objective response rates (ORR) of 13.3% with a median progression-free survival (PFS) of 4.2 months for EGFR E20ins and 35.3% with 4.7 months for HER2 E20ins, respectively. In contrast, novel EGFR E20ins-targeted agents exhibited an ORR of 46.2% with a median PFS of 5.4 months, while HER2-targeted agents showed an ORR of 50% with that of 7.0 months.
Conclusion
Identification of EGFR and HER2 E20ins is more important as their targeted therapies improved outcomes. Upfront NGS test as a comprehensive molecular approach is strongly warranted.

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Clinical Outcomes of EGFR Exon 20 Insertion Mutations in Advanced Non-small Cell Lung Cancer in Korea: Seonggyu Byeon, Youjin Kim, Sung Won Lim, Jang Ho Cho, Sehoon Park, Jiyun Lee, Jong-Mu Sun, Yoon-La Choi, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn; Cancer Res Treat. 2019;51(2):623-631. Published online July 23, 2018; DOI: https://doi.org/10.4143/crt.2018.151

Abstract PDF Supplementary Material PubReader ePub

Purpose
Epidermal growth factor receptor (EGFR) exon 20 insertion mutations account for approximately 4% of all EGFR mutations. Given the rarity of this mutation, its clinical outcomes are not fully established.
Materials and Methods
Between 2009 and 2017, non-small cell lung cancer (NSCLC) patients who showed an exon 20 insertion were retrospectively reviewed for clinical characteristics and outcomes, including responses to chemotherapy (CTx) or targeted therapy.
Results
Of 3,539 NSCLC patients who harbored an activating EGFR mutation, 56 (1.6%) had an exon 20 insertion. Of the advanced NSCLC patients, 27 of 1,479 (1.8%) had an exon 20 insertion. The median overall survival was 29.4 months (95% confidence interval 9.3 to 49.6) for 27 advancedNSCLC patients. The 22 patientswho received systemic CTx achieved a 50.0% response rate and a 77.2% disease control rate, with 4.2 months of progressionfree survival. Six patients received EGFR tyrosine kinase inhibitors (TKIs). Three of the four patients that had only an exon 20 insertion showed progressive disease, while one showed stable disease. The othertwo patients had an exon 20 insertion and another EGFR mutation and achieved a partial response.
Conclusion
The incidence of an exon 20 insertion mutation is rare in Korea and occasionally accompanied by other common EGFR mutations. Although the response to systemic CTx. in these patients is comparable to that of patients with other mutations, the response rate to firstor second-generation EGFR TKIs is quite low. Therefore, the development of a more efficient agent is urgently needed.

Citations

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Pasi A. Jänne, Bin-Chao Wang, Byoung Chul Cho, Jun Zhao, Juan Li, Maximilian Hochmair, Solange Peters, Benjamin Besse, Nick Pavlakis, Joel W. Neal, Terufumi Kato, Yi-Long Wu, Danny Nguyen, Junjing Lin, Jianchang Lin, Florin Vranceanu, Annette Szumski, Hua
Journal of Clinical Oncology.2025;[Epub] CrossRef
The combination of immune checkpoint inhibitor and chemotherapy may be efficacious for advanced non-small cell lung cancer with near-loop insertions of EGFR exon 20: A retrospective analysis
Ke-Jun Liu, Hong-Rui Li, Quan-Quan Tan, Tao Jiang, Kai-Cheng Peng, Hua-Jun Chen, Qing Zhou, Xu-Chao Zhang, Zheng Zheng, Shi-Yuan Chen, Xue Zheng, Hong-Bo Zheng, Bei-Bei Mao, Long-Long Gong, Xian-Wen Chen, Wendy Wu, Yi-Long Wu, Jun Jia, Jin-Ji Yang
Science Progress.2025;[Epub] CrossRef
Advances in the Diagnosis and Treatment of Advanced Non–Small-Cell Lung Cancer With EGFR Exon 20 Insertion Mutation
Jingwen Liu, Yan Xiang, Tingwen Fang, Lulin Zeng, Ao Sun, Yixiang Lin, Kaihua Lu
Clinical Lung Cancer.2024; 25(2): 100. CrossRef
Unmet needs in EGFR exon 20 insertion mutations in Central and Eastern Europe: reimbursement, diagnostic procedures, and treatment availability
Maximilian J. Hochmair, Mojca Unk, Jelena Spasic, Timur Cerić, Assia Konsoulova, Mircea Dediu, Krisztina Bogos, Alinta Hegmane, Kersti Oselin, Marko Stojiljkovic, Tina Roblek, Marko Jakopovic
BMC Proceedings.2024;[Epub] CrossRef
Clinical outcomes in patients with non-small cell lung cancer harboring EGFR Exon20 in-frame insertions in the near-loop and far-loop: Results from LC-SCRUM-Asia
Masanobu Okahisa, Hibiki Udagawa, Shingo Matsumoto, Terufumi Kato, Hiroshi Yokouchi, Naoki Furuya, Ryota Kanemaru, Ryo Toyozawa, Akihiro Nishiyama, Kadoaki Ohashi, Shingo Miyamoto, Kazumi Nishino, Atsushi Nakamura, Eiji Iwama, Seiji Niho, Hajime Oi, Tetsu
Lung Cancer.2024; 191: 107798. CrossRef
The current landscape, advancements, and prospects in the treatment of patients with EGFR exon 20 insertion mutations warrant scientific elucidation
Xiuyue Man, Xueru Sun, Chen Chen, Yan Xiang, Jing Zhang, Lei Yang
Frontiers in Oncology.2024;[Epub] CrossRef
Real-life comparison of afatinib and erlotinib in non-small cell lung cancer with rare EGFR exon 18 and exon 20 mutations: a Turkish Oncology Group (TOG) study
Pınar Gursoy, Ali Murat Tatli, Dilek Erdem, Erdem Goker, Emir Celik, Nebi Serkan Demirci, Abdullah Sakin, Muhammed Mustafa Atci, Ertuğrul Bayram, Tuğba Akın Telli, Burak Bilgin, Ahmet Bilici, Baran Akangunduz, Sevinç Balli, Ahmet Demirkazik, Fatih Selçukb
Journal of Cancer Research and Clinical Oncology.2023; 149(2): 865. CrossRef
Comparative effectiveness of mobocertinib and standard of care in patients with NSCLC with EGFR exon 20 insertion mutations: An indirect comparison
Sai-Hong I. Ou, Huamao M. Lin, Jin-Liern Hong, Yu Yin, Shu Jin, Jianchang Lin, Minal Mehta, Pingkuan Zhang, Danny Nguyen, Joel W. Neal
Lung Cancer.2023; 179: 107186. CrossRef
EGFR and ERBB2 exon 20 insertion/duplication in advanced non–small cell lung cancer: genomic profiling and clinicopathologic features
Ramakrishna R. Sompallae, Bilge Dundar, Natalya V. Guseva, Aaron D. Bossler, Deqin Ma
Frontiers in Oncology.2023;[Epub] CrossRef
Characteristics, treatment patterns, and clinical outcomes in patients with advanced non-small cell lung cancer harboring EGFR exon 20 insertions
Ying-Ting Liao, Lei-Chi Wang, Ruei-Lin Sun, Yi-Chen Yeh, Hsu-Ching Huang, Chia-I Shen, Yen-Han Tseng, Tsu-Hui Hsiao, Heng-Sheng Chao, Yung-Hung Luo, Yuh-Min Chen, Chi-Lu Chiang
Journal of Cancer Research and Clinical Oncology.2023; 149(12): 10365. CrossRef
EGFR exon20 insertion mutations in non-small cell lung cancer: Clinical implications and recent advances in targeted therapies
Qianming Bai, Jialei Wang, Xiaoyan Zhou
Cancer Treatment Reviews.2023; 120: 102605. CrossRef
A comprehensive overview of the heterogeneity of EGFR exon 20 variants in NSCLC and (pre)clinical activity to currently available treatments
Fenneke Zwierenga, Bianca A.M.H. van Veggel, Anke van den Berg, Harry J.M. Groen, Lili Zhang, Matthew R. Groves, K. Kok, E.F. Smit, T. Jeroen N. Hiltermann, Adrianus J. de Langen, Anthonie J. van der Wekken
Cancer Treatment Reviews.2023; 120: 102628. CrossRef
Epidemiological characteristics and therapeutic advances of EGFR exon 20 insertion mutations in non‐small cell lung cancer
Binyang Pan, Jiaqi Liang, Haochun Shi, Kungeng Rao, Weigang Guo, Cheng Zhan
Thoracic Cancer.2023; 14(33): 3247. CrossRef
Aumolertinib-based comprehensive treatment for an uncommon site of EGFR exon 20 insertion mutations with multiple metastases non-small cell lung cancer: a case report
Youjun Deng, Chenglin Yang, Wenyi Liu, Songhua Cai, Xiaotong Guo
Anti-Cancer Drugs.2022; 33(4): 406. CrossRef
Population pharmacokinetics of mobocertinib in healthy volunteers and patients with non–small cell lung cancer
Neeraj Gupta, Philippe B. Pierrillas, Michael J. Hanley, Steven Zhang, Paul M. Diderichsen
CPT: Pharmacometrics & Systems Pharmacology.2022; 11(6): 731. CrossRef
Amivantamab and Mobocertinib in Exon 20 insertions EGFR Mutant Lung Cancer, Challenge To The Current Guidelines
Timothée Olivier, Vinay Prasad
Translational Oncology.2022; 23: 101475. CrossRef
Poziotinib for EGFR exon 20-mutant NSCLC: Clinical efficacy, resistance mechanisms, and impact of insertion location on drug sensitivity
Yasir Y. Elamin, Jacqulyne P. Robichaux, Brett W. Carter, Mehmet Altan, Hai Tran, Don L. Gibbons, Simon Heeke, Frank V. Fossella, Vincent K. Lam, Xiuning Le, Marcelo V. Negrao, Monique B. Nilsson, Anisha Patel, R.S.K. Vijayan, Jason B. Cross, Jianjun Zhan
Cancer Cell.2022; 40(7): 754. CrossRef
EGFR exon 20 insertion variants A763_Y764insFQEA and D770delinsGY confer favorable sensitivity to currently approved EGFR-specific tyrosine kinase inhibitors
Guangjian Yang, Yaning Yang, Jiaqi Hu, Haiyan Xu, Shuyang Zhang, Yan Wang
Frontiers in Pharmacology.2022;[Epub] CrossRef
The mechanism of action of different generations of EGFR-inhibitors in malignant lung tumors. Literature review and data synthesis
Ainur F. Nasretdinov, Konstantin V. Menshikov, Alexander V. Sultanbaev, Shamil I. Musin, Nadezda I. Sultanbaeva, Irina A. Men'shikova
Journal of Modern Oncology.2022; 24(3): 340. CrossRef
Mobocertinib (TAK-788) in EGFR Exon 20 Insertion+ Metastatic NSCLC: Patient-Reported Outcomes from EXCLAIM Extension Cohort
Maria Garcia Campelo, Caicun Zhou, Suresh Ramalingam, Huamao Lin, Tae Kim, Gregory Riely, Tarek Mekhail, Danny Nguyen, Erin Goodman, Minal Mehta, Sanjay Popat, Pasi Jänne
Journal of Clinical Medicine.2022; 12(1): 112. CrossRef
Osimertinib for Chinese advanced non-small cell lung cancer patients harboring diverse EGFR exon 20 insertion mutations
Guang-Jian Yang, Jun Li, Hai-Yan Xu, Yang Sun, Liu Liu, Hong-Shuai Li, Lu Yang, Yuan Zhang, Guo-Hui Li, Yan Wang
Lung Cancer.2021; 152: 39. CrossRef
Epidemiological and clinical burden of EGFR Exon 20 insertion in advanced non-small cell lung cancer: A systematic literature review
Heather Burnett, Helena Emich, Chris Carroll, Naomi Stapleton, Parthiv Mahadevia, Tracy Li, Rama Krishna Kancha
PLOS ONE.2021; 16(3): e0247620. CrossRef
Response to Standard Therapies and Comprehensive Genomic Analysis for Patients with Lung Adenocarcinoma with EGFR Exon 20 Insertions
Noura J. Choudhury, Adam J. Schoenfeld, Jessica Flynn, Christina J. Falcon, Hira Rizvi, Charles M. Rudin, Mark G. Kris, Maria E. Arcila, Glenn Heller, Helena A. Yu, Marc Ladanyi, Gregory J. Riely
Clinical Cancer Research.2021; 27(10): 2920. CrossRef
EGFR Exon 20 Insertion Mutations: Clinicopathological Characteristics and Treatment Outcomes in Advanced Non–Small Cell Lung Cancer
Jose Luis Leal, Marliese Alexander, Malinda Itchins, Gavin M. Wright, Steven Kao, Brett G.M. Hughes, Nick Pavlakis, Stephen Clarke, Anthony J Gill, Hannah Ainsworth, Benjamin Solomon, Thomas John
Clinical Lung Cancer.2021; 22(6): e859. CrossRef
Activity and Safety of Mobocertinib (TAK-788) in Previously Treated Non–Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations from a Phase I/II Trial
Gregory J. Riely, Joel W. Neal, D. Ross Camidge, Alexander I. Spira, Zofia Piotrowska, Daniel B. Costa, Anne S. Tsao, Jyoti D. Patel, Shirish M. Gadgeel, Lyudmila Bazhenova, Viola W. Zhu, Howard L. West, Tarek Mekhail, Ryan D. Gentzler, Danny Nguyen, Sylv
Cancer Discovery.2021; 11(7): 1688. CrossRef
Clinical characteristics of advanced non-small cell lung cancer patients with EGFR exon 20 insertions
Chie Morita, Tatsuya Yoshida, Masayuki Shirasawa, Ken Masuda, Yuji Matsumoto, Yuki Shinno, Shigehiro Yagishita, Yusuke Okuma, Yasushi Goto, Hidehito Horinouchi, Noboru Yamamoto, Noriko Motoi, Yasushi Yatabe, Yuichiro Ohe
Scientific Reports.2021;[Epub] CrossRef
EGFR Exon 20 Insertion in Metastatic Non-Small-Cell Lung Cancer: Survival and Clinical Efficacy of EGFR Tyrosine-Kinase Inhibitor and Chemotherapy
Samy Chelabi, Xavier Mignard, Karen Leroy, Isabelle Monnet, Solenn Brosseau, Nathalie Theou-Anton, Marie-Ange Massiani, Sylvie Friard, Boris Duchemann, Elizabeth Fabre, Etienne Giroux-Leprieur, Jacques Cadranel, Marie Wislez
Cancers.2021; 13(20): 5132. CrossRef
Treatment Outcomes and Safety of Mobocertinib in Platinum-Pretreated Patients With EGFR Exon 20 Insertion–Positive Metastatic Non–Small Cell Lung Cancer
Caicun Zhou, Suresh S. Ramalingam, Tae Min Kim, Sang-We Kim, James Chih-Hsin Yang, Gregory J. Riely, Tarek Mekhail, Danny Nguyen, Maria R. Garcia Campelo, Enriqueta Felip, Sylvie Vincent, Shu Jin, Celina Griffin, Veronica Bunn, Jianchang Lin, Huamao M. Li
JAMA Oncology.2021; 7(12): e214761. CrossRef
A Real-World Study of Patients with Advanced Non-squamous Non-small Cell Lung Cancer with EGFR Exon 20 Insertion: Clinical Characteristics and Outcomes
Christos Chouaid, Thomas Filleron, Didier Debieuvre, Maurice Pérol, Nicolas Girard, Eric Dansin, Hervé Lena, Radj Gervais, Sophie Cousin, Josiane Otto, Roland Schott, David Planchard, Anne Madroszyk, Courèche Kaderbhai, Pascale DUBRAY-Longeras, Sandrine H
Targeted Oncology.2021; 16(6): 801. CrossRef
External Quality Assurance of Current Technology for the Testing of Cancer-Associated Circulating Free DNA Variants
Sze Yee Chai, Rongxue Peng, Rui Zhang, Li Zhou, Nalishia Pillay, Kwang Hong Tay, Tony Badrick, Jinming Li, Martin P. Horan
Pathology & Oncology Research.2020; 26(3): 1595. CrossRef
Osimertinib treatment for patients with EGFR exon 20 mutation positive non-small cell lung cancer
B. van Veggel, J.F. Vilacha Madeira R Santos, S.M.S. Hashemi, M.S. Paats, K. Monkhorst, D.A.M. Heideman, M. Groves, T. Radonic, E.F. Smit, E. Schuuring, A.J. van der Wekken, A.J. de Langen
Lung Cancer.2020; 141: 9. CrossRef
EGFR exon 20 insertion mutations in Chinese advanced non-small cell lung cancer patients: Molecular heterogeneity and treatment outcome from nationwide real-world study
Guangjian Yang, Jun Li, Haiyan Xu, Yaning Yang, Lu Yang, Fei Xu, Bing Xia, Viola W. Zhu, Misako Nagasaka, Yan Yang, Yapin Li, Weini Qiu, Jianming Ying, Sai-Hong Ignatius Ou, Yan Wang
Lung Cancer.2020; 145: 186. CrossRef
Variability of EGFR exon 20 insertions in 24 468 Chinese lung cancer patients and their divergent responses to EGFR inhibitors
YanRu Qin, Hong Jian, Xiaoling Tong, Xue Wu, Fufeng Wang, Yang W. Shao, Xinmin Zhao
Molecular Oncology.2020; 14(8): 1695. CrossRef
The effectiveness of afatinib in patients with lung adenocarcinoma harboring complex epidermal growth factor receptor mutation
Shang-Gin Wu, Chong-Jen Yu, James Chih-Hsin Yang, Jin-Yuan Shih
Therapeutic Advances in Medical Oncology.2020;[Epub] CrossRef
Spectrum of uncommon and compound epidermal growth factor receptor mutations in non-small-cell lung carcinomas with treatment response and outcome analysis: A study from India
Varsha Singh, Aruna Nambirajan, Prabhat Singh Malik, Sanjay Thulkar, Ravindra Mohan Pandey, Kalpana Luthra, Sudheer Arava, Ruma Ray, Anant Mohan, Deepali Jain
Lung Cancer.2020; 149: 53. CrossRef
Effectiveness of Treatments for Advanced Non–Small-Cell Lung Cancer With Exon 20 Insertion Epidermal Growth Factor Receptor Mutations
Jenn-Yu Wu, Chong-Jen Yu, Jin-Yuan Shih
Clinical Lung Cancer.2019; 20(6): e620. CrossRef
Clinical outcome of treatment of metastatic non-small cell lung cancer in patients harboring uncommon EGFR mutation
J. Chantharasamee, N. Poungvarin, P. Danchaivijitr, S. Techawatanawanna
BMC Cancer.2019;[Epub] CrossRef
Finding the Right Way to Target EGFR in Glioblastomas; Lessons from Lung Adenocarcinomas
Ya Gao, Wies R. Vallentgoed, Pim J. French
Cancers.2018; 10(12): 489. CrossRef

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