Tarceva Approved by the FDA as Single-Agent Treatment for Advanced NSCLC

ROCKVILLE, Maryland-After priority review, the US Foodand Drug Administration (FDA) hasapproved Tarceva tablets (erlotinib,OSI Pharmaceuticals) as a singleagenttreatment for patients with locallyadvanced or metastatic non-small-cell lung cancer (NSCLC)whose disease has continued toprogress despite other therapies, includingat least one prior chemotherapyregimen. The FDA grantedmarketing approval on the basis ofincreased survival findings in theTarceva-treated arm of a phase IIItrial in patients who had receivedsecond- or third-line therapy for advancedNSCLC."FDA believes it is crucial for cancerpatients to have many safe andeffective treatment options in theirbattle against this disease" saidLester M. Crawford, MD, ActingFDA Commissioner. "With the approvalof Tarceva, thousands of patientswith lung cancer will not onlyhave access to another treatmentoption, but one that extends life."Tarceva, which is distributed byGenentech, is an epidermal growthfactor receptor (EGFR) inhibitor;while it is known to block the tyrosinekinase associated with EGFR,the mechanism of action by which itexerts its clinical benefit is not completelyunderstood. It is the first ofits class to demonstrate a survivaladvantage for advanced NSCLC in aphase III trial. However, two large,randomized studies of Tarceva givenconcurrently with doublet platinum-based chemotherapy (carboplatin[Paraplatin] and paclitaxel orgemcitabine [Gemzar] and cisplatin)to patients with previously untreatedadvanced NSCLC failed to showclinical benefit, and the drug is notrecommended for such use.The pivotal clinical study onwhich the FDA based its approvaldecision for Tarceva was conductedby the National Cancer Institute ofCanada Clinical Trials Group, basedat Queen's University, Kingston,Ontario, Canada, in collaborationwith OSI Pharmaceuticals. It involved731 patients with locally advancedor metastatic NSCLC in arandomized, double-blind, placebocontrolledtrial conducted in 17countries. Patients were randomized2:1 to Tarceva 150 mg or to placebo,given orally once daily until diseaseprogression or unacceptable toxicityoccurred.

Study ResultsThe primary endpoint and all secondaryendpoints of the trial weremet. Survival, progression-free survival,and tumor response all provedto be significant in favor of Tarceva(P = < .001). Median survival time,evaluated in an intent-to-treat population,was 6.7 months for Tarcevavs 4.7 months for placebo. Medianprogression-free survival time was9.9 weeks vs 7.9 weeks, respectively,and the Tarceva-treated patients hada tumor response rate of 8.9%, vs0.9% for placebo. One-year survivalwas 31.2% in the treatment groupvs 21.5% for the control patients,and median duration of responsewas 34.3 weeks vs 15.9 weeks, respectively.Subgroup AnalysesA series of patient subsets of wereexamined in exploratory univariateanalyses. Tarceva's survival effect wassimilar across most subsets, althoughin two subsets, a larger survival effectwas observed (EGFR-positive patientsand patients who never smoked).Among the 238 patients with aknown EGFR status, the 78 EGFRpositiveTarceva patients had a bettersurvival rate than the 49 EGFR-posi-tive placebo patients (hazard ratio[HR] = 0.65). Tarceva did not appearto affect survival in the EGFR-negativesubgroup (HR = 1.01). A survivalbenefit due to Tarceva in the EGFRnegativesubgroup cannot be excluded,however, because the confidenceintervals for the EGFR-positive, -negative,and unmeasured subgroups arewide and overlap (see Table 1).Nonsmokers in the study whowere EGFR-positive had a largeTarceva survival benefit (HR = 0.27).Twenty percent (146) of the studyparticipants had never smoked.Tumor responses were observed inall EGFR subgroups.The most common grade 3-4 adverseevents in the Tarceva-treatedpatients were rash (9%) and diarrhea(6%).