On May 14, 2013, the U. S. Food and Drug Administration approved erlotinib (Tarceva, Astellas Pharma Inc.) for the first-line treatment of metastatic non-small cell lung cancer (NSCLC) patients whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations.  This indication for erlotinib is being approved concurrently with the cobas EGFR Mutation Test, a companion diagnostic test for patient selection. The approval was based on the results of a randomized, multicenter, open label trial comparing erlotinib (n=86) to platinum-based doublet chemotherapy (n=88) in patients with metastatic NSCLC whose tumors had EGFR exon 19 deletions or exon 21 (L858R) substitution mutations determined by a clinical trial assay (CTA). Eligible patients were randomly allocated (1:1) to receive erlotinib, 150 mg/day orally, or platinum-based doublet chemotherapy. Randomization was stratified by EGFR mutation (exon 19 deletion or exon 21 (L858R) substitution) and ECOG PS (0 vs. 1 vs. 2). Tumor samples from 134 patients were tested retrospectively by the cobas® EGFR Mutation Test. 

The trial’s primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS) and objective response rate (ORR). The median age of patients was 65 years.  The majority of the patients were female (72%), Caucasian (99%), never-smokers (69%), and had adenocarcinoma histology (93%). The median PFS was 10.4 months in the erlotinib arm and 5.2 months in the platinum-based chemotherapy arm
[HR 0.34 (95% CI: 0.23, 0.49), p <0.001].  The median OS was 22.9 months in the erlotinib arm and 19.5 months in the platinum-based chemotherapy arm [HR 0.93 (95% CI: 0.64, 1.35), p=0.6482].  The ORR was 65% in the erlotinib arm and 16% in the platinum-based chemotherapy arm.  The majority of the patients in the platinum-based chemotherapy arm (82%) subsequently received an EGFR tyrosine kinase inhibitor following investigator-determined disease progression.  Analysis of PFS in the cobas EGFR Mutation Test positive patients was consistent with the primary analysis.
The most frequent (≥ 30%) adverse reactions of any grade in the erlotinib arm were rash, diarrhea, asthenia, cough, dyspnea and decreased appetite. The most frequent (≥ 5%) grade 3-4 adverse reactions in the erlotinib arm were rash and diarrhea.
The recommended daily dose of erlotinib for NSCLC is 150 mg taken orally at least one hour before or two hours after the ingestion of food.  Treatment should continue until disease progression or unacceptable toxicity.  Full prescribing information is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021743s018lbl.pdf