Erlotinib Shows Promise as First-Line Therapy, Phase II Data Show

ORLANDO, Florida-Erlotinib(Tarceva) alone demonstratedsignificant activity as first-line chemotherapyagainst advanced nonsmall-cell lung cancer (NSCLC) in aphase II trial conducted in The Netherlands,France, and Switzerland. Thefindings showed that the tyrosine kinase(TK) inhibitor had efficacy similarto that observed with the mostactive cytotoxic agents, said coinvestigatorJean-Charles Soria, MD, PhD,of the division of cancer medicine,Institute Gustave Roussy, Villejuif,France (abstract 7073).The trial enrolled 54 patients withstage IIIb or IV NSCLC who had nothad previous chemotherapy. Participantsreceived 150 mg of erlotinib perday until disease progression or unacceptabletoxicity.Durable ResponsesAt 6 weeks, 55% of patients hadeither a complete response, partial response,or stable disease. Among the23% with complete or partial responses,the median duration of responsewas 256 days (Table 1).The majority of the responses occurredin women, never smokers, andpatients with adenocarcinoma and/orbronchioalveolar carcinoma, Dr. Soriasaid. However, responses were alsoobserved in men, current smokers, andpatients with squamous cell carcinoma.The one complete response occurredin a male current/former smokerwith adenocarcinoma.Tissue samples were available foronly five of the responders, and justone of those had the epidermal growthfactor receptor (EGFR) mutations associatedwith response to TK inhibi-tors. Mutations in the K-ras gene werefound only in patients who did notrespond to erlotinib, Dr. Soria said.Overall, adverse effects were mild.Diarrhea and rash were most common,including grade 3 rash in threepatients and grade 3 diarrhea in twopatients. There were no grade 4 toxicities.Three patients discontinuedtreatment because of side effects andfive had their dose reduced to 100 mg.Study ImplicationsThis is one of the first studies oferlotinib as first-line therapy in a generalpopulation of NSCLC patients,said Roman Perez-Soler, MD, chief ofthe oncology division in the departmentof medicine at Montefiore MedicalCenter, New York. As the discussantof this trial and of otherinvestigations of TK inhibitors, henoted that the only other trial of firstlineerlotinib was in elderly patients.

"Despite the favorable demographics,I think the response rate appearshigher than that observed in secondlinestudies," Dr. Perez-Soler said. Theimplication of the findings, he said, isthat as a single agent, erlotinib may beas active as the classical chemotherapyagents and could now be tested asfirst-line therapy in a phase III trialcomparing it with standard chemotherapyin selected patients.