U.S. Food and Drug Administration Approval Summary: Erlotinib for the First-Line Treatment of Metastatic Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor Exon 19 Deletions or Exon 21 (L858R) Substitution Mutations

Abstract

On May 14, 2013, the U.S. Food and Drug Administration approved erlotinib (Tarceva, Astellas Pharma Inc., Northbrook, IL, http://www.us.astellas.com/) for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations. This indication for erlotinib was approved concurrently with the cobas EGFR Mutation Test (Roche Molecular Systems, Inc., Basel, Switzerland, http:// www.molecular.roche.com), a companion diagnostic test for patient selection. The approval was based on clinically important improvements in progression-free survival (PFS) and objective response rate (ORR) and an acceptable toxicity profile demonstrated in a multicenter, open label trial enrolling 174 patients with metastatic NSCLC whose tumors had EGFR mutations as determined by a laboratorydeveloped test. Patients were randomized (1:1) to receive erlotinib (150 mg/day) or platinum-based doublet chemotherapy. The primary endpoint was investigator-assessed PFS. Secondary endpoints included overall survival (OS) and ORR. Superior PFS (hazard ratio [HR] 0.34; 95% confidence interval [CI]: 0.23, 0.49; p , .001) and ORR (65% vs. 16%) were observed in the erlotinib arm. Median PFS was 10.4 months and 5.2 months in the erlotinib and chemotherapy arms, respectively. There was no difference in OS (HR 0.93; 95% CI: 0.64, 1.35) with median OS of 22.9 months and 19.5 months in the erlotinib and chemotherapy arms, respectively. The most frequent ($30%) adverse reactions in the erlotinib-treated patients were rash, diarrhea, asthenia, cough, dyspnea, and decreased appetite. The most frequent ($5%) grade 3 and 4 adverse reactions were rash and diarrhea. The Oncologist 2014;19:774-779 Implications for Practice: In this report, we present key information on the U.S. Food and Drug Administration approval of erlotinib for the first-line treatment of patients with metastatic non-small cell lung cancer whose tumors have epidermal growth factor receptor exon 19 deletions or exon 21 (L858R) substitution mutations. We discuss the data supporting the approval decision, highlighting the importance of molecular enrichment in establishing the effectiveness of erlotinib as first-line therapy in metastatic non-small cell lung cancer.

Eyelash trichomegaly following treatment with erlotinib in a non-small cell lung cancer patient: A case report and literature review

“…Recently, with the wide use of erlotinib in NSCLC patients, an increased number of cutaneous adverse effects, including acneiform rash or pruritus, have been observed (6). Erlotinib-associated eyelash trichomegaly has been reported only in a small number of case reports (4,5,(15)(16)(17).…”

“…With the wide use of EGFR tyrosine kinase inhibitors (TKIs) in patients with NSCLC, an increasing number of side effects have been observed, including skin rash, diarrhea, stomatitis and eyelash trichomegaly (4,5). The adverse events most frequently reported by erlotinib-treated patients are rash (56.0%) and diarrhea (62.0%) (6). Although erlotinib exhibits a number of side effects, it presents significant clinical benefits in the treatment of non-small cell lung cancer (NSCLC), particularly in patients with an EGFR mutation (6).…”

“…The adverse events most frequently reported by erlotinib-treated patients are rash (56.0%) and diarrhea (62.0%) (6). Although erlotinib exhibits a number of side effects, it presents significant clinical benefits in the treatment of non-small cell lung cancer (NSCLC), particularly in patients with an EGFR mutation (6). Recently, the FDA approved the use of erlotinib as first-line therapy in patients with exon 19 deletions or exon 21 (L858R) substitution mutations (6).…”

“…Although erlotinib exhibits a number of side effects, it presents significant clinical benefits in the treatment of non-small cell lung cancer (NSCLC), particularly in patients with an EGFR mutation (6). Recently, the FDA approved the use of erlotinib as first-line therapy in patients with exon 19 deletions or exon 21 (L858R) substitution mutations (6). Eyelash trichomegaly, which was first identified by Gray et al (7) in 1944, is characterized by the increased length, thickness, stiffness, curling and pigmentation of the eyelashes.…”

Harnessing plasma genotyping for precision therapy against lung cancer

“…In the absence of EGFR mutation or gene amplification, there is no significant difference in the responses to the treatment with EGFR inhibitors and conventional chemotherapies (12). Thus, EGFR gene mutation test is mandatory for using EGFR antagonists as the firstline treatment for advanced NSCLC (13). Consequently, genetic profiling of surgical and biopsy samples is routinely performed clinically for lung cancer patients to provide guidance for selection of treatment regimens.…”