J Thorac Oncol. 2013 Jan 29. [Epub ahead of print]
Epidermal Growth Factor Receptor Inhibition in Lung Cancer: Status 2012.
Hirsch FR, Jänne PA, Eberhardt WE, Cappuzzo F, Thatcher N, Pirker R, Choy H, Kim ES, Paz-Ares L, Gandara DR, Wu YL, Ahn MJ, Mitsudomi T, Shepherd FA,Mok TS.
Source
*Department of Medicine, Division of Medical Oncology and Department of Pathology, University of Colorado Cancer Center, Aurora, Colorado; †Dana-Farber Cancer Institute, Lowe Center for Thoracic Oncology, Boston, Massachusetts; ‡Department of Medicine (Cancer Research), West German Cancer Center, Essen, Germany; §Department of Oncology, Instituto Toscano Tumori, Ospedale Civile, Livorno, Italy; ‖Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, United Kingdom; ¶Department of Medicine I, Medical University Vienna, Vienna, Austria; #Department of Therapeutic Radiation Oncology, The University of Texas Southwestern Medical Center, Dallas, Texas; **Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas; ††Department of Medicine, Instituto de Biomedicina de Sevilla, University Hospital Virgen del Rocío, Seville, Spain; ‡‡Department of Internal Medicine, Division of Hematology/Oncology and Department of Radiation Oncology, UC Davis CancerCenter, Sacramento, California; §§Department of Medicine, Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China; ‖‖Department of Medicine, Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; ¶¶Department of Surgery, Division of Thoracic Surgery, Kinki University School of Medicine, Japan; ##Department of Medicine, Division of Medical Oncology and Hematology, University Health Network, Princess Margaret Hospital and the University of Toronto, Toronto, Canada; and ***Department of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
Abstract
Lung cancer is the most common cause of cancer deaths. Most patients present with advanced-stage disease, and the prognosis is generally poor. However, with the understanding of lung cancer biology, and development of molecular targeted agents, there have been improvements in treatment outcomes for selected subsets of patients with non-small-cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated significantly improved tumor responses and progression-free survival in subsets of patients with advanced NSCLC, particularly those with tumors harboring activating EGFR mutations. Testing for EGFR mutations is a standard procedure for identification of patients who will benefit from first-line EGFR TKIs. For patients with advanced NSCLC and no activating EGFR mutations (EGFR wild-type) or no other driving oncogenes such as ALK-gene rearrangement, chemotherapy is still the standard of care. A new generation of EGFR TKIs, targeting multiple receptors and with irreversible bindings to the receptors, are in clinical trials and have shown encouraging effects. Research on primary and acquired resistant mechanisms to EGFR TKIs are ongoing. Monoclonal antibodies (e.g. cetuximab), in combination with chemotherapy, have demonstrated improved outcomes, particularly for subsets of NSCLC patients, but further validations are needed. Novel monoclonal antibodies are combined with chemotherapy, and randomized comparative studies are ongoing. This review summarizes the current status of EGFR inhibitors in NSCLC in 2012 and some of the major challenges we are facing.
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