In-Jae Oh1, Jae Young Hur2, Cheol-Kyu Park1, Young-Chul Kim1, Seung Joon Kim3, Min Ki Lee4, Hee Joung Kim5, Kye Young Lee5, Jae Cheol Lee6, Chang-Min Choi7. 1. Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea; Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, Jeonnam, Korea. 2. Lung Cancer Center, Konkuk University Medical Center, Seoul, Korea; Department of Pathology, Konkuk University Medical Center, Seoul, Korea. 3. Department of Internal Medicine, The Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea. 4. Department of Internal Medicine, Pusan National University Hospital, Busan, Korea. 5. Lung Cancer Center, Konkuk University Medical Center, Seoul, Korea; Department of Pulmonary Medicine, Konkuk University School of Medicine, Seoul, Korea. 6. Department of Oncology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea. 7. Department of Oncology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea; Department of Pulmonology and Critical Care Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea. Electronic address: ccm@amc.seoul.kr.
Abstract
INTRODUCTION: HER2 mutations are found in 2% to 4% of non-small-cell lung cancer cases and are usually mutually exclusive with other genetic alterations. We screened a large cohort of patients from multiple institutions in Korea, described the characteristics of HER2-mutant cases, and reported on several patients who were treated with pan-HER inhibitors. PATIENTS AND METHODS: The study population consisted of 360 patients diagnosed with adenocarcinoma from 4 institutions in Korea from June 2015 to September 2016. Tissue specimens from all participants were screened by direct sequencing, and next-generation sequencing was conducted only on specimens that were positive in direct sequencing. HER2-targeted therapy, either poziotinib or afatinib, was orally administrated. RESULTS: Next-generation sequencing was conducted in 129 patients, and finally 29 (8.1%) patients with HER2 mutation were identified. Most patients were female (58.6%), had never smoked (70.0%), and had stage IV non-small-cell lung cancer (55.2%). For all patients, the histologic type was adenocarcinoma, with no coexisting EGFR or ALK alterations. The most common type of HER2 mutation (48.3%) was c.2326_2327insTGT in exon 20. A partial response was observed in 2 patients who received poziotinib and 1 patient who received afatinib. The main toxicities of the pan-HER inhibitors were nausea, diarrhea, and mucositis. CONCLUSION: HER2 mutation was estimated at a frequency of approximately 8.1% in Korean patients with adenocarcinoma in the absence of known driver mutations. Because some of the HER2-mutant cases responded to poziotinib or afatinib, further studies are warranted.
INTRODUCTION:HER2 mutations are found in 2% to 4% of non-small-cell lung cancer cases and are usually mutually exclusive with other genetic alterations. We screened a large cohort of patients from multiple institutions in Korea, described the characteristics of HER2-mutant cases, and reported on several patients who were treated with pan-HER inhibitors. PATIENTS AND METHODS: The study population consisted of 360 patients diagnosed with adenocarcinoma from 4 institutions in Korea from June 2015 to September 2016. Tissue specimens from all participants were screened by direct sequencing, and next-generation sequencing was conducted only on specimens that were positive in direct sequencing. HER2-targeted therapy, either poziotinib or afatinib, was orally administrated. RESULTS: Next-generation sequencing was conducted in 129 patients, and finally 29 (8.1%) patients with HER2 mutation were identified. Most patients were female (58.6%), had never smoked (70.0%), and had stage IV non-small-cell lung cancer (55.2%). For all patients, the histologic type was adenocarcinoma, with no coexisting EGFR or ALK alterations. The most common type of HER2 mutation (48.3%) was c.2326_2327insTGT in exon 20. A partial response was observed in 2 patients who received poziotinib and 1 patient who received afatinib. The main toxicities of the pan-HER inhibitors were nausea, diarrhea, and mucositis. CONCLUSION:HER2 mutation was estimated at a frequency of approximately 8.1% in Korean patients with adenocarcinoma in the absence of known driver mutations. Because some of the HER2-mutant cases responded to poziotinib or afatinib, further studies are warranted.
Authors: W Victoria Lai; Louisiane Lebas; Tristan A Barnes; Julie Milia; Ai Ni; Oliver Gautschi; Solange Peters; Roberto Ferrara; Andrew J Plodkowski; John Kavanagh; Joshua K Sabari; Stephen J Clarke; Nick Pavlakis; Alexander Drilon; Charles M Rudin; Maria E Arcila; Natasha B Leighl; Frances A Shepherd; Mark G Kris; Julien Mazières; Bob T Li Journal: Eur J Cancer Date: 2019-01-24 Impact factor: 9.162
Authors: Jacqulyne P Robichaux; Yasir Y Elamin; R S K Vijayan; Monique B Nilsson; Lemei Hu; Junqin He; Fahao Zhang; Marlese Pisegna; Alissa Poteete; Huiying Sun; Shuai Li; Ting Chen; Han Han; Marcelo Vailati Negrao; Jordi Rodon Ahnert; Lixia Diao; Jing Wang; Xiuning Le; Funda Meric-Bernstam; Mark Routbort; Brent Roeck; Zane Yang; Victoria M Raymond; Richard B Lanman; Garrett M Frampton; Vincent A Miller; Alexa B Schrock; Lee A Albacker; Kwok-Kin Wong; Jason B Cross; John V Heymach Journal: Cancer Cell Date: 2019-10-03 Impact factor: 31.743