Impact of HER2 aberrations on EGFR-TKI treatment outcomes in lung tumors harboring EGFR mutations: A HER2-CS STUDY subset analysis.

person Hiroe Kayatani Respiratory Medicine, National Hospital Organization Okayama Medical Center, Okayama, Japan info_outline Hiroe Kayatani, Kadoaki Ohashi, Hiroshige Yoshioka, Akihiro Bessho, Nobuhisa Ishikawa, Masahiro Yamasaki, Toshiyuki Kozuki, Nobukazu Fujimoto, Yutaka Ueda, Syuuji Bandoh, Isao Murakami, Hirohisa Ichikawa, Tetsuya Kubota, Keisuke Sugimoto, Nagio Takigawa, Takashi Sumikawa, Katsuyuki Kiura, Keisuke Aoe

Authors person Hiroe Kayatani Respiratory Medicine, National Hospital Organization Okayama Medical Center, Okayama, Japan info_outline Hiroe Kayatani, Kadoaki Ohashi, Hiroshige Yoshioka, Akihiro Bessho, Nobuhisa Ishikawa, Masahiro Yamasaki, Toshiyuki Kozuki, Nobukazu Fujimoto, Yutaka Ueda, Syuuji Bandoh, Isao Murakami, Hirohisa Ichikawa, Tetsuya Kubota, Keisuke Sugimoto, Nagio Takigawa, Takashi Sumikawa, Katsuyuki Kiura, Keisuke Aoe Organizations Respiratory Medicine, National Hospital Organization Okayama Medical Center, Okayama, Japan, Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan, Department of Thoracic Oncology, Kansai Medical University Hospital, Hirakata, Japan, Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital, Okayama, Japan, Department of Respiratory Medicine, Hiroshima Prefectural Hospital, Hiroshima, Japan, Hiroshima Red Cross and Atomic-Bomb Survivors Hospital, Hiroshima, Japan, Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan, Department of Medical Oncology, Okayama Rosai Hospital, Okayama, Japan, Department of Respiratory Medicine, Kagawa Prefectural Central Hospital, Takamatsu, Japan, Faculty of Medicine, Kagawa University, Kitagun, Japan, National Hospital Organization Higashihiroshima Medical Center, Higashi-Hiroshima, Japan, Department of Respiratory Medicine, KKR Takamatsu Hospital, Takamatsu, Japan, Department of Hematology and Respiratory Medicine, Kochi Medical School, Kochi University, Kochi, Japan, Department of Respiratory Medicine, Kobe Red Cross Hospital, Kobe, Japan, Department of General Internal Medicine 4, Kawasaki Medical School, Okayama, Japan, Tottori Prefectural Central Hospital, Tottori, Japan, Department of Allergy and Respiratory Medicine, Okayama University Hospital, Okayama, Japan, National Hospital Organization Yamaguchi-Ube Medical Center, Ube, Japan Abstract Disclosures Research Funding Other Government Agency Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are a key treatment for EGFR-mutated non-small-cell lung carcinoma (NSCLC). To date, a biomarker to predict whether NSCLC will exhibit a short- or long-term response to first- or second-generation EGFR-TKIs has not been established for clinical use. Human epidermal growth factor receptor-2 (HER2) aberrations are mechanisms for acquired resistance to EGFR-TKIs; however, their impact on EGFR-TKI therapy outcomes in EGFR-mutant NSCLC has not yet been systematically evaluated. Methods: Patients with advanced NSCLC were prospectively registered from more than 35 institutes (HER2-CS STUDY UMIN 000017003). EGFR mutations or anaplastic lymphoma kinase gene translocations were assessed at each institution using a commercially approved test. HER2 protein expression levels were determined by immunohistochemistry (IHC) using the Ventana I-VIEW PATHWAY anti-HER-2/neu (4B5). The IHC status scoring system applied to gastric cancer was used. Results: Of 1,126 screened patients with NSCLC, 354 (31.8%) had EGFR-mutated tumors, and the HER2 protein statuses were as follows: IHC0 (n = 71, 26%), IHC1+ (n = 148, 53%), IHC2+ (n = 51, 18%), and IHC3+ (n = 7, 3%). The patients’ demographics were almost identical in those with lung tumors harboring EGFR mutations and HER2-IHC2+/3+ (group P) or EGFR mutations and HER2-IHC0/1 (group N). The EGFR-TKI response rates were not different between these groups (Table). However, group P showed significantly shorter time to EGFR-TKI treatment failure than group N (median 19.1 vs. 13.3 months; log rank p = 0.038). Conclusions: These data from a large prospective cohort show that HER2 protein expression in EGFR-mutant NSCLC may have a negative impact on the effect of EGFR-TKIs. A clinical trial of EGFR/HER2-TKIs (e.g., afatinib) is warranted for this population. Group N Group P IHC 0 (n = 71) IHC 1+ (n = 148) IHC 2+ (n = 51) IHC 3+ (n = 7) Complete Response 4 6 1 0 Partial Response 45 83 33 4 Stable Disease 8 36 10 2 Progressive Disease 3 9 5 1 Not Evaluated 4 14 2 0 Overall response rate 69% 60% 67% 57% Disease control rate 80% 84% 86% 86% Time to treatment failure (months) 19.1 13.1