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Osimertinib in Japanese patients with EGFR T790M mutation-positive advanced non-small-cell lung cancer: AURA3 trial.
Cancer Sci 2018; 109(6):1930-1938CS

Abstract

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.).

Authors+Show Affiliations

Third Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan.Institute of Biomedical Research and Innovation, Kobe, Japan.Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan.Graduate School of Medicine, Kyoto University, Kyoto, Japan.Osaka International Cancer Institute, Osaka, Japan.Yokohama City University Medical Center, Yokohama, Japan.AstraZeneca, Royston, Hertfordshire, UK.AstraZeneca, Osaka, Japan.Aichi Cancer Center Hospital, Nagoya, Japan.

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

29697876

Citation

Akamatsu, Hiroaki, et al. "Osimertinib in Japanese Patients With EGFR T790M Mutation-positive Advanced Non-small-cell Lung Cancer: AURA3 Trial." Cancer Science, vol. 109, no. 6, 2018, pp. 1930-1938.
Akamatsu H, Katakami N, Okamoto I, et al. Osimertinib in Japanese patients with EGFR T790M mutation-positive advanced non-small-cell lung cancer: AURA3 trial. Cancer Sci. 2018;109(6):1930-1938.
Akamatsu, H., Katakami, N., Okamoto, I., Kato, T., Kim, Y. H., Imamura, F., ... Hida, T. (2018). Osimertinib in Japanese patients with EGFR T790M mutation-positive advanced non-small-cell lung cancer: AURA3 trial. Cancer Science, 109(6), pp. 1930-1938. doi:10.1111/cas.13623.
Akamatsu H, et al. Osimertinib in Japanese Patients With EGFR T790M Mutation-positive Advanced Non-small-cell Lung Cancer: AURA3 Trial. Cancer Sci. 2018;109(6):1930-1938. PubMed PMID: 29697876.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Osimertinib in Japanese patients with EGFR T790M mutation-positive advanced non-small-cell lung cancer: AURA3 trial. AU - Akamatsu,Hiroaki, AU - Katakami,Nobuyuki, AU - Okamoto,Isamu, AU - Kato,Terufumi, AU - Kim,Young Hak, AU - Imamura,Fumio, AU - Shinkai,Masaharu, AU - Hodge,Rachel A, AU - Uchida,Hirohiko, AU - Hida,Toyoaki, Y1 - 2018/05/31/ PY - 2017/12/22/received PY - 2018/03/15/revised PY - 2018/03/29/accepted PY - 2018/4/27/pubmed PY - 2018/6/21/medline PY - 2018/4/27/entrez KW - Japanese KW - epidermal growth factor receptor KW - mutation KW - non-small-cell lung cancer KW - tyrosine kinase SP - 1930 EP - 1938 JF - Cancer science JO - Cancer Sci. VL - 109 IS - 6 N2 - 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.). SN - 1349-7006 UR - https://www.unboundmedicine.com/medline/citation/29697876/Osimertinib_in_Japanese_patients_with_EGFR_T790M_mutation_positive_advanced_non_small_cell_lung_cancer:_AURA3_trial_ L2 - https://doi.org/10.1111/cas.13623 DB - PRIME DP - Unbound Medicine ER -