In NSCLC, Second-Line Gefitinib Is as Effective as Docetaxel, but Less Toxic

LJUBLJANA, Slovenia-Gefitinib(Iressa) has similar efficacy andlow toxicity compared with docetaxel(Taxotere) in the second-line treatmentof advanced non-small-cell lungcancer (NSCLC), results of the Second-line Indication of Gefitinib inNSCLC (SIGN) study indicate. Thetrial was the first to compare the twodrugs in this palliative setting, saidTanja Cufer, MD, of the Institute ofOncology, Ljubljana, Slovenia, andcolleagues (abstract 7035).Currently approved drugs for second-line therapy of advanced NSCLCare docetaxel, erlotinib (Tarceva), andpemetrexed (Alimta).Striking Differencesin Adverse EventsAmong the 139 evaluable patientsin this international, phase II study,there were grade 3 and 4 adverse eventsin 8.9% of the patients on gefitinib vs25.4% of those on docetaxel. Grade 3and 4 neutropenia was 46% with docetaxelvs 1.6% with gefitinib, and leukopeniarates were 37.3% vs 0. Grade3 and 4 rash and diarrhea, which areassociated with tyrosine kinase inhibitors(TKIs), were no worse on thegefitinib arm of the trial.Symptom andQOL BenefitSymptom and quality of life (QOL)improvements were somewhat higherin the gefitinib arm. About 26% of thepatients on docetaxel experiencedimprovements in symptoms and inQOL. Of the patients on gefitinib,36.9% had symptom improvementand 33.8% reported QOL improvement.Though these differences were notstatistically significant, they did suggestimprovement. "There does appearto be a trend toward improvement[in symptoms and QOL] in thegefitinib arm as opposed to docetaxel,"said discussant Charles Rudin,MD, PhD, director of the Lung CancerTherapeutics Program, SidneyKimmel Comprehensive CancerCenter.Comparable ResponsesResponse and survival rates werevery similar for the two drugs. Theobjective response rate was 13.2% forgefitinib and 13.7% for docetaxel;median overall survival was 7.5months for gefitinib and 7.1 monthsfor docetaxel; and median progres-sion-free survival time was 3.0 monthswith gefitinib and 3.4 months withdocetaxel."I think the conclusion perhaps isnot surprising...EGFR TKIs may offerimproved quality of life with similaroutcomes relative to cytotoxicchemotherapies for non-small-celllung cancer," Dr. Rudin said. "So thesedata really are consistent with Dr.Shepherd's BR.21 study using Tarceva."Further ComparisonsWarrantedThe investigators concluded thatthe findings support further comparisonsof the two drugs. A phase IIIstudy, the Iressa NSCLC Trial EvaluatingResponse and Survival againstTaxotere (INTEREST) has alreadybeen initiated, using the same design.Dr. Rudin noted that other agentsunder study in this population includecetuximab (Erbitux) as monotherapy,docetaxel with gefitinib, and docetaxelwith bortezomib (Velcade).