1. Pharmacokinetic drug evaluation of osimertinib for the treatment of non-small cell lung cancer
- Author
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G. Palomba, Evaristo Maiello, Gerardo Sanpaolo, Antonio Rossi, Cristiano Carbonelli, Concetta Di Micco, Paolo Graziano, Vito D'Alessandro, Marco Taurchini, Lucia Anna Muscarella, and Stefano Notarangelo
- Subjects
0301 basic medicine ,Lung Neoplasms ,Afatinib ,Antineoplastic Agents ,Toxicology ,Piperazines ,03 medical and health sciences ,T790M ,0302 clinical medicine ,Gefitinib ,Epidermal growth factor ,Carcinoma, Non-Small-Cell Lung ,medicine ,Humans ,heterocyclic compounds ,Osimertinib ,Rociletinib ,Protein Kinase Inhibitors ,neoplasms ,Pharmacology ,Acrylamides ,Aniline Compounds ,integumentary system ,business.industry ,General Medicine ,respiratory tract diseases ,ErbB Receptors ,030104 developmental biology ,030220 oncology & carcinogenesis ,Mutation ,Icotinib ,Disease Progression ,Cancer research ,Erlotinib ,business ,medicine.drug - Abstract
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.
- Published
- 2017