Pharmacokinetic drug evaluation of osimertinib for the treatment of non-small cell lung cancer. (2nd December 2017)

• Record Type: Journal Article
• Authors: Rossi, Antonio; Muscarella, Lucia Anna; Di Micco, Concetta; Carbonelli, Cristiano; D'alessandro, Vito; Notarangelo, Stefano; Palomba, Giuseppe; Sanpaolo, Gerardo; Taurchini, Marco; Graziano, Paolo; Maiello, Evaristo
• Is Part Of: Expert opinion on drug metabolism and toxicology. Volume 13:Number 12(2017:Dec.)
• Page Start: 1281
• Page End: 1288
• Publication Date: 2017-12-02
• Subjects: Afatinib -- EGFR -- erlotinib -- gefitinib -- icotinib -- NSCLC -- osimertinib -- rociletinib -- T790M -- ulmutinib; Drugs -- Toxicology -- Periodicals; Drugs -- Metabolism -- Periodicals; 615.7
• DOI: 10.1080/17425255.2017.1401064
• Languages: English
• ISSNs: 1742-5255

Abstract

ABSTRACT: Introduction : First- and second-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, erlotinib, icotinib, and afatinib are the standard-of-care for first-line therapy of non-small-cell lung cancer (NSCLC) harboring activating EGFR mutations. Unfortunately, after initial activity of an average 9–13 months, disease progression has been reported in the majority of patients. In about 50% of cases the progression is due to the onset of the T790M mutation in exon 20 of the EGFR gene. Third-generation EGFR-TKIs targeting this mutation were investigated, with osimertinib the only reaching clinical practice. Areas covered : A structured search of bibliographic databases for peer-reviewed research literature and of main meetings using a focused review question addressing osimertinib, was undertaken. Expert opinion : Osimertinib is the standard-of-care for EGFR -mutated patients progressing to first-line EGFR-TKIs due to the acquired EGFR T790M mutation. Results from the head-to-head first-line trial comparing osimertinib versus gefitinib or erlotinib in activating EGFR mutations might change the front-line approach. Osimertinib in combination regimens, such as immunotherapy, and in adjuvant setting are ongoing. Thus, the strategic approach for the management of EGFR -mutated NSCLC patients will change further in the next few years.