ORLANDO, Florida-Erlotinib (Tarceva) alone demonstrated significant activity as first-line chemotherapy against advanced nonsmall- cell lung cancer (NSCLC) in a phase II trial conducted in The Netherlands, France, and Switzerland. The findings showed that the tyrosine kinase (TK) inhibitor had efficacy similar to that observed with the most active cytotoxic agents, said coinvestigator Jean-Charles Soria, MD, PhD, of the division of cancer medicine, Institute Gustave Roussy, Villejuif, France (abstract 7073). The trial enrolled 54 patients with stage IIIb or IV NSCLC who had not had previous chemotherapy. Participants received 150 mg of erlotinib per day until disease progression or unacceptable toxicity. Durable Responses At 6 weeks, 55% of patients had either a complete response, partial response, or stable disease. Among the 23% with complete or partial responses, the median duration of response was 256 days (Table 1). The majority of the responses occurred in women, never smokers, and patients with adenocarcinoma and/or bronchioalveolar carcinoma, Dr. Soria said. However, responses were also observed in men, current smokers, andpatients with squamous cell carcinoma. The one complete response occurred in a male current/former smoker with adenocarcinoma. Tissue samples were available for only five of the responders, and just one of those had the epidermal growth factor receptor (EGFR) mutations associated with response to TK inhibi-tors. Mutations in the K-ras gene were found only in patients who did not respond to erlotinib, Dr. Soria said. Overall, adverse effects were mild. Diarrhea and rash were most common, including grade 3 rash in three patients and grade 3 diarrhea in two patients. There were no grade 4 toxicities. Three patients discontinued treatment because of side effects and five had their dose reduced to 100 mg. Study Implications This is one of the first studies of erlotinib as first-line therapy in a generalpopulation of NSCLC patients, said Roman Perez-Soler, MD, chief of the oncology division in the department of medicine at Montefiore Medical Center, New York. As the discussant of this trial and of other investigations of TK inhibitors, he noted that the only other trial of firstline erlotinib was in elderly patients. "Despite the favorable demographics, I think the response rate appears higher than that observed in secondline studies," Dr. Perez-Soler said. The implication of the findings, he said, is that as a single agent, erlotinib may be as active as the classical chemotherapy agents and could now be tested as first-line therapy in a phase III trial comparing it with standard chemotherapy in selected patients.