title: Trastuzumab Emtansine in HER2+ Recurrent Metastatic Non-Small-Cell Lung Cancer: Study Protocol.
abstract: The treatment outcome has been unsatisfactory for patients with non-small-cell lung cancer (NSCLC) refractory to standard first-line chemotherapy. Trastuzumab emtansine (T-DM1), an anti-HER2 antibody conjugated with a vinca alkaloid, has been approved for clinical use in HER2+ breast cancer in many countries. Approximately 5% of NSCLC tumors possess HER2 alterations, and T-DM1 has shown excellent antitumor effects against HER2+ lung cancer cell lines in preclinical models. Therefore, we hypothesized that T-DM1 could significantly inhibit the growth of HER2+ lung cancers. We have launched a nonrandomized phase II trial of T-DM1 monotherapy for patients with HER2+ lung cancers. The major eligibility criteria are as follows: age ≥ 20 years, pathologically diagnosed NSCLC with documented HER2 positivity (immunohistochemistry 3+, both immunohistochemistry 2+ and fluorescence in situ hybridization positive, or exon 20 insertion mutation), and previous chemotherapy. Thirty patients will receive T-DM1 3.6 mg/kg every 3 weeks. The primary endpoint is the overall response rate. This trial will provide information on whether T-DM1 monotherapy is effective against HER2+ lung cancer.
authors: Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan. Electronic address: kohashi@cc.okayama-u.ac.jp.
authors: Kadoaki
authors: K
authors: Ohashi
authors: Center of Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan.
authors: Katsuyuki
authors: K
authors: Hotta
authors: Center of Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan.
authors: Taizo
authors: T
authors: Hirata
authors: Department of Medical Oncology, National Hospital Organization Yamaguchi-Ube Medical Center, Yamaguchi, Japan.
authors: Keisuke
authors: K
authors: Aoe
authors: Department of Thoracic Oncology and Medicine, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan.
authors: Toshiyuki
authors: T
authors: Kozuki
authors: Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Kiichiro
authors: K
authors: Ninomiya
authors: Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Hiroe
authors: H
authors: Kayatani
authors: Department of Pathology, Okayama University Hospital, Okayama, Japan.
authors: Hiroyuki
authors: H
authors: Yanai
authors: Department of Clinical Genomic Medicine, Okayama University, Okayama, Japan.
authors: Shinichi
authors: S
authors: Toyooka
authors: Center of Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan.
authors: Shiro
authors: S
authors: Hinotsu
authors: Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Kyoto University, Kyoto, Japan.
authors: Minoru
authors: M
authors: Takata
authors: Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
authors: Katsuyuki
authors: K
authors: Kiura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult; D000080044:Ado-Trastuzumab Emtansine; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D005500:Follow-Up Studies; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008453:Maytansine / Q000031:analogs & derivatives / Q000627:therapeutic use; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D000068878:Trastuzumab
chemical_list: D000080044:Ado-Trastuzumab Emtansine; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D008453:Maytansine; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: HER2 amplification; HER2 mutations; HER2 over-expression; NSCLC; Trastuzumab emtansine