Overview of the current status of human epidermal growth factor receptor inhibitors in lung cancer.
Although chemotherapy remains the standard of care for lung cancer, new less toxic drugs are urgently needed. Targeted agents represent a new era in cancer therapy, and non-small-cell lung cancer (NSCLC) is at the forefront of many development programs. An exciting target is the human epidermal growth factor receptor (EGFR, ie, HER1), and agents targeting this receptor, including gefitinib, cetuximab, and erlotinib (OSI-774; Tarceva), are being investigated. These agents have antitumor activity and are less toxic than most therapies. Based on phase II data, gefitinib received US approval for third-line treatment of patients with locally advanced or metastatic NSCLC. Cetuximab is licensed in the United States for patients with metastatic colorectal carcinoma. However, erlotinib, recently approved in the United States for second- and third-line treatment of patients with locally advanced or metastatic NSCLC, is the only agent of this class to improve survival as monotherapy in patients with advanced, refractory NSCLC, as shown in a phase III placebo-controlled trial. Phase III trials of erlotinib and gefitinib combined with chemotherapy were disappointing, which could be the result of drug scheduling, chemotherapy combinations, or other factors. Patient characteristics may also affect outcome, and research is ongoing to identify predictive markers of response to enable patient selection and improve outcome. Recently identified mutations within the HER1/EGFR tyrosine kinase (TK) domain may provide insight into why some patients respond rapidly to HER1/EGFR tyrosine kinase inhibitors. Surrogate markers of efficacy are also being investigated, including rash, which could be used to monitor and optimize antitumor activity. Therefore, although more work is required, data indicate that HER1/EGFR inhibitors will play an important role in treating patients with NSCLC.
Herbst
Roy S
RS
Department of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston , TX 77030, USA. rherbst@mdanderson.org
Sandler
Alan B
AB
D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000628:therapy; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000628:therapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors