No data available.
Please log in to see this content.
You have no subscription access to this content.
The full text of this article is not currently available.
非小細胞肺癌における新規EGFR チロシンキナーゼ不可逆的阻害剤Osimertinib−基礎と臨床−
Rent:
Rent this article for
JPY
Abstract
Osimertinib is an oral, potent, irreversible EGFR tyrosine kinase inhibitor that is selective for EGFR tyrosine kinase inhibitor-sensitizing mutations and the T790M resistance mutation. This mono-anilino-pyrimidine compound is structurally distinct and offers a pharmacologically differentiated profile from other EGFR-TKIs. As compared with previous EGFR inhibitors, osimertinib shows less in vitro activity against wild-type EGFR. In studies involving in vivo xenograft and genetically engineered mouse models representing EGFR sensitizing and T790M mutant disease, osimertinib demonstrated durable tumour shrinkage. Phase I study (NCT01802632)was conducted with the primary objective of determining the safety, tolerability and efficacy of osimertinib in patients with advanced EGFR-mutated NSCLC whose disease had progressed on prior therapy with an EGFR-TKI. Among 31 patients enrolled in the dose-escalation cohorts, no dose-limiting toxic effects occurred at doses of 20-240 mg once daily. An additional 222 patients were treated in expansion cohorts. We found that osimertinib was associated with a response rate of 61% among 127 patients with EGFR T790M, with limited skin and gastrointestinal adverse effects. This suggests that a structurally distinct EGFR inhibitor, one that is selective for the mutated form of EGFR, can be clinically effective and has a side-effect profile that is not dose-limiting in the majority of patients in whom T790M-mediated drug resistance had developed. Osimertinib received approval as the treatment for patients with EGFR T790M mutation-positive metastatic NSCLC in the US, EU and Japan. Osimertinib is being compared with platinum-based doublet chemotherapy in the confirmatory Phase III study in patients with EGFR T790M mutation-positive metastatic NSCLC who have progressed after EGFR-TKI therapy(NCT02151981)
Full text loading...
/content/article/0386-3603/44060/839