Beyond the TRIBUTE trial: integrating HER1/EGFR tyrosine kinase inhibitors with chemotherapy in advanced NSCLC.
Evaluation of: Herbst RS, Prager D, Hermann R et al.: TRIBUTE: a Phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small cell lung cancer. J. Clin. Oncol. 23, 5892-5899 (2005). Patients diagnosed with advanced non-small cell lung cancer have limited therapeutic options. A large, randomized, controlled trial of the human epidermal growth factor receptor tyrosine-kinase inhibitor, erlotinib (Tarceva), plus standard first-line chemotherapy did not meet its primary end point of improved survival in the overall population, but did reveal a striking survival benefit in a subset of patients who had never smoked. There are a number of possible explanations for the lack of overall benefit, including the use of an unselected patient population, the need for alternatives to concurrent administration, and a postulated pathophysiological interaction between erlotinib and chemotherapy. Ongoing studies investigating alternative schedules and sequences of administration with chemotherapy will help clinicians to determine how agents such as erlotinib can best be combined with standard cytotoxic agents.
Department of Thoracic Oncology, Hospital Grosshansdorf, Woehrendamn 80, 22927 Grosshansdorf, Germany. dr.martin.reck@web.de
Martin
M
Reck
D000971:Antineoplastic Combined Chemotherapy Protocols; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D018450:Disease Progression; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012907:Smoking; D013534:Survival; D016896:Treatment Outcome; D015854:Up-Regulation
D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D016190:Carboplatin; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D017239:Paclitaxel