Flipped script for gefitinib: A reapproved tyrosine kinase inhibitor for first-line treatment of epidermal growth factor receptor mutation positive metastatic nonsmall cell lung cancer

Abstract

Purpose The approval history, pharmacology, pharmacokinetics, clinical trials, efficacy, dosing recommendations, drug interactions, safety, place in therapy, and economic considerations of gefitinib are reviewed. Summary Lung cancer is one of the most commonly diagnosed cancers and is the leading cause of cancer death. Platinum-based chemotherapy and tyrosine kinase inhibitors, such as erlotinib and afatinib, are recommended therapies for nonsmall cell lung cancer. The European Medicines Association based their approval of gefitinib on the randomized, multicenter Iressa Pan-Asia Study (IPASS, NCT00322452) and a single-arm study showing effectiveness in Caucasians (IFUM, NCT01203917). Both studies were recently referenced by the United States Food & Drug Administration to reapprove gefitinib for the first-line treatment of advanced nonsmall cell lung cancer with epidermal growth factor receptor exon 19 deletions or exon 21 substitution. Diarrhea, acneiform rash, and interstitial lung disease are known side effects of gefitinib. Conclusion Use of gefitinib for the first-line therapy of metastatic nonsmall cell lung cancer with epidermal growth factor receptor exon 19 deletions (residues 747-750) or exon 21 substitution mutation (L858R) is well-documented and supported.

Histopathological transformation to small-cell lung carcinoma in non-small cell lung carcinoma tumors

“…The use of modern therapies for lung cancer such as tyrosine kinase inhibitors (TKIs), some of which inhibit EGFR and others ALK, has improved survival in patients with specific genetic anomalies of their tumors (19)(20)(21). These treatments are preferred over standard intravenous chemotherapy, not only because of their advantages in terms of outcomes, but also because of the better quality of life that patients report.…”

Brain metastasis in non-small cell lung cancer (NSCLC) patients with uncommon EGFR mutations: a report of seven cases and literature review

“…Six cases received systemic chemotherapy as the first-line therapy, while case 2 received brain radiotherapy instead. Brain radiotherapy combined with EGFR-TKIs seems to be the standard therapy and is well tolerated in patients with BM of EGFR-mutated NSCLC 5 , 8 , 12 , 30 - 36 . Intracranial PFS was improved in patients receiving upfront radiotherapy compared with those receiving upfront EGFR-TKI (37.9 vs. 10.6 months; P < 0.001) 37 .…”

“…The survival time of these patients is approximately 7–12 months 3 , 4 , according to recent reports. EGFR- tyrosine kinase inhibitors (TKIs) are frequently used as a standard treatment of BM from EGFR-mutation positive NSCLC 5 , 6 . Patients with uncommon EGFR mutations have lower response rates to EGFR-TKIs than those who have more common mutations.…”

The economic case for precision medicine

“…Subsequent trial evidence revealed heterogeneity in response to gefitinib that was unobserved previously, with respect to EGFR-TK mutation status [45]. The FDA and European Medicines Agency, consequently, granted marketing authorization for gefitinib in patients with NSCLC that had activating mutations of EGFR-TK [46]. The economic case for gefitinib is based on the premise of improved clinical effectiveness by stratifying the population of NSCLC patients by EGFR-TK mutation status.…”