FDA Approves Tarceva in Second-Line Tx

ROCKVILLE, Maryland—The Food and Drug Administration(FDA) has approved Tarceva tablets(erlotinib, OSI Pharmaceuticals) as asingle-agent treatment for patientswith locally advanced or metastaticnon-small-cell lung cancer (NSCLC)whose disease has continued toprogress despite other therapies, includingat least one prior chemotherapyregimen. The FDA granted marketingapproval on the basis ofincreased survival findings in theTarceva-treated arm of a phase III trialin patients who had received second-or third-line therapy for advanced NSCLC. The primary endpointof the study was overall survival.Secondary endpoints includedprogression-free survival and tumorresponse rate.Tarceva, developed by OSI anddistributed by Genentech, is an epidermalgrowth factor receptor (EGFR)inhibitor, and it is the first of the classto demonstrate a survival advantagefor advanced NSCLC in a phase IIItrial. However, two large, randomizedstudies of Tarceva given concurrentlywith doublet platinum-basedchemotherapy in previously untreatedadvanced NSCLC failed to show clinical benefit, and the drug is notrecommended for such use.The pivotal study involved 731 patientswith locally advanced or metastaticNSCLC in a randomized,double-blind, placebo-controlledtrial conducted in 17 countries. Patientswere randomized 2:1 to receiveTarceva 150 mg or placebo, administeredorally once daily until diseaseprogression or unacceptable toxicity.Survival, progression-free survival,and tumor response all proved significantin favor of Tarceva (P < .001).Median survival, evaluated in an intent-to-treat population, was 6.7months for Tarceva vs 4.7 months forplacebo. Median progression-free survivalwas 9.9 vs 7.9 weeks, respectively,and the Tarceva-treated patients had a tumor response rate of 8.9% vs0.9% for placebo. One-year survivalwas 31.2% in the treatment group vs21.5% for the control patients, andmedian duration of response was 34.3vs 15.9 weeks, respectively.

EGFR status was not part of thestudy protocol, and survival was seenin a broad range of patients. Survivalamong EGFR-positive patients waslooked at retrospectively, however.Among the 238 patients with a knownEGFR status, the 78 EGFR-positiveTarceva-treated patients had a bettersurvival rate than the 49 EGFR-positiveplacebo patients. Tarceva did notappear to affect survival in the EGFRnegativesubgroup (HR = 1.01). Asurvival benefit due to Tarceva in theEGFR-negative subgroup cannot beexcluded, however, because the confidenceintervals for the EGFR-positive,-negative, and unmeasuredsubgroups are wide and overlap (seeTable 1).The most common adverse reactionsin patients receiving Tarcevawere rash and diarrhea.