Osimertinib in Japanese patients with EGFR T790M mutation-positive advanced non-small-cell lung cancer: AURA3 trial

Autor: Nobuyuki Katakami, Rachel Hodge, Masaharu Shinkai, Terufumi Kato, Isamu Okamoto, Toyoaki Hida, Hiroaki Akamatsu, Fumio Imamura, Hirohiko Uchida, Young Hak Kim
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Oncology
Cancer Research
Lung Neoplasms
Piperazines
T790M
0302 clinical medicine
Japan
Carcinoma
Non-Small-Cell Lung
Antineoplastic Combined Chemotherapy Protocols
Medicine
Osimertinib
Epidermal growth factor receptor
non‐small‐cell lung cancer
Aged
80 and over
Aniline Compounds
biology
Hazard ratio
tyrosine kinase
Anemia
General Medicine
Middle Aged
ErbB Receptors
Pemetrexed
030220 oncology & carcinogenesis
Female
Tyrosine kinase
medicine.drug
Adult
Diarrhea
medicine.medical_specialty
Disease-Free Survival
Young Adult
03 medical and health sciences
Asian People
Internal medicine
Humans
Adverse effect
Lung cancer
Protein Kinase Inhibitors
Aged
Platinum
Acrylamides
business.industry
medicine.disease
respiratory tract diseases
030104 developmental biology
Mutation
Japanese
biology.protein
epidermal growth factor receptor
business
Zdroj: Cancer Science. 109:1930-1938
ISSN: 1347-9032
DOI: 10.1111/cas.13623
Popis: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the first-line treatment for patients with EGFR mutant non-small-cell lung cancer (NSCLC). However, most patients become resistant to these drugs, so their disease progresses. Osimertinib, a third-generation EGFR-TKI that can inhibit the kinase even when the common resistance-conferring Thr790Met (T790M) mutation is present, is a promising therapeutic option for patients whose disease has progressed after first-line EGFR-TKI treatment. AURA3 was a randomized (2:1), open-label, phase III study comparing the efficacy of osimertinib (80 mg/d) with platinum-based therapy plus pemetrexed (500 mg/m2 ) in 419 patients with advanced NSCLC with the EGFR T790M mutation in whom disease had progressed after first-line EGFR-TKI treatment. This subanalysis evaluated the safety and efficacy of osimertinib specifically in 63 Japanese patients enrolled in AURA3. The primary end-point was progression-free survival (PFS) based on investigator assessment. Improvement in PFS was clinically meaningful in the osimertinib group (n = 41) vs the platinum-pemetrexed group (n = 22; hazard ratio 0.27; 95% confidence interval, 0.13-0.56). The median PFS was 12.5 and 4.3 months in the osimertinib and platinum-pemetrexed groups, respectively. Grade ≥3 adverse events determined to be related to treatment occurred in 5 patients (12.2%) treated with osimertinib and 12 patients (54.5%) treated with platinum-pemetrexed. The safety and efficacy results in this subanalysis are consistent with the results of the overall AURA3 study, and support the use of osimertinib in Japanese patients with EGFR T790M mutation-positive NSCLC whose disease has progressed following first-line EGFR-TKI treatment. (ClinicalTrials.gov trial registration no. NCT02151981.).
Databáze: OpenAIRE
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