PMID- 31265163 OWN - NLM STAT- MEDLINE DCOM- 20190930 LR - 20220603 IS - 1349-7006 (Electronic) IS - 1347-9032 (Print) IS - 1347-9032 (Linking) VI - 110 IP - 9 DP - 2019 Sep TI - Osimertinib for Japanese patients with T790M-positive advanced non-small-cell lung cancer: A pooled subgroup analysis. PG - 2884-2893 LID - 10.1111/cas.14120 [doi] AB - Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are the standard of care for non-small-cell lung cancer (NSCLC) patients harboring EGFR mutations. However, almost all patients develop resistance after approximately 1 y of treatment, with >50% of cases due to the T790M secondary mutation of the EGFR gene. A large global Phase III study (AURA3) demonstrated that osimertinib significantly prolonged progression-free survival (PFS) over platinum-doublet chemotherapy in patients with T790M-positive NSCLC who had progressed on previous EGFR-TKI therapy. However, it is not clear whether efficacy or safety of osimertinib in Japanese patients is similar to the overall population. We report a pre-planned subgroup analysis of pooled Phase II data from the AURA Extension and AURA2 trials to investigate the efficacy and safety of osimertinib in Japanese patients. This study included 81 Japanese patients. Patients were administered 80 mg osimertinib orally once daily until disease progression. The main endpoints were objective response rate (ORR), PFS, and safety. The ORR was 63.6% and median PFS was 13.8 mo. Overall survival rate at 36 mo was 54.0%. The most common all-cause adverse events (AEs) were rash (grouped term; 65.4%), diarrhea (51.9%), paronychia (grouped term; 49.4%), and dry skin (grouped term; 39.5%). Most AEs were grade 1-2. Five patients (6.2%) developed interstitial lung disease, resulting in two deaths (2.5%). Osimertinib demonstrated favorable ORR and PFS in Japanese patients, similar to the overall population. Additionally, osimertinib has good efficacy and a manageable safety profile in Japanese patients with NSCLC who had acquired resistance due to the T790M mutation. CI - (c) 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. FAU - Hirashima, Tomonori AU - Hirashima T AD - Department of Thoracic Oncology, Osaka Habikino Medical Center, Habikino-city, Osaka, Japan. FAU - Satouchi, Miyako AU - Satouchi M AD - Department of Thoracic Oncology, Hyogo Cancer Center, Akashi, Hyogo, Japan. FAU - Hida, Toyoaki AU - Hida T AUID- ORCID: 0000-0003-3537-0020 AD - Department of Thoracic Oncology, Aichi Cancer Center Hospital, Chikusa-ku, Nagoya, Japan. FAU - Nishio, Makoto AU - Nishio M AUID- ORCID: 0000-0003-4969-4165 AD - Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan. FAU - Kato, Terufumi AU - Kato T AD - Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Kanazawa-ku, Yokohama, Japan. FAU - Sakai, Hiroshi AU - Sakai H AD - Department of Thoracic Oncology, Saitama Cancer Center, Ina, Kita-adachi-gun, Saitama, Japan. FAU - Imamura, Fumio AU - Imamura F AD - Department of Thoracic Oncology, Osaka International Cancer Institute, Chuo-ku, Osaka, Japan. FAU - Kiura, Katsuyuki AU - Kiura K AD - Department of Allergy and Respiratory Medicine, Okayama University Hospital, Kita-ku, Okayama, Japan. FAU - Okamoto, Isamu AU - Okamoto I AUID- ORCID: 0000-0002-7587-6096 AD - Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan. FAU - Kasahara, Kazuo AU - Kasahara K AD - Department of Respiratory Medicine, Kanazawa University Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa, Ishikawa, Japan. FAU - Uchida, Hirohiko AU - Uchida H AD - Research and Development, AstraZeneca K.K., Kita-ku, Osaka, Japan. FAU - Vowler, Sarah L AU - Vowler SL AD - Global Medicines Development, AstraZeneca, Cambridge, UK. FAU - Mitsudomi, Tetsuya AU - Mitsudomi T AUID- ORCID: 0000-0001-9860-8505 AD - Division of Thoracic Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan. LA - eng GR - AstraZeneca/ PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20190801 PL - England TA - Cancer Sci JT - Cancer science JID - 101168776 RN - 0 (Acrylamides) RN - 0 (Aniline Compounds) RN - 0 (Antineoplastic Agents) RN - 0 (Protein Kinase Inhibitors) RN - 3C06JJ0Z2O (osimertinib) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Acrylamides/*administration & dosage/adverse effects MH - Administration, Oral MH - Adult MH - Aged MH - Aged, 80 and over MH - Aniline Compounds/*administration & dosage/adverse effects MH - Antineoplastic Agents/*administration & dosage/adverse effects MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics/mortality/pathology MH - Diarrhea/chemically induced/epidemiology MH - Disease Progression MH - Drug Resistance, Neoplasm/drug effects/genetics MH - ErbB Receptors/antagonists & inhibitors/genetics MH - Exanthema/chemically induced/epidemiology MH - Humans MH - Japan/epidemiology MH - Lung Diseases, Interstitial/chemically induced/epidemiology MH - Lung Neoplasms/*drug therapy/genetics/mortality/pathology MH - Middle Aged MH - Paronychia/chemically induced/epidemiology MH - Progression-Free Survival MH - Protein Kinase Inhibitors/*administration & dosage/adverse effects MH - Survival Analysis MH - Survival Rate PMC - PMC6726692 OTO - NOTNLM OT - EGFR mutation OT - acquired resistance OT - non-small-cell lung cancer OT - osimertinib OT - tyrosine kinase inhibitor EDAT- 2019/07/03 06:00 MHDA- 2019/10/01 06:00 PMCR- 2019/09/01 CRDT- 2019/07/03 06:00 PHST- 2019/02/25 00:00 [received] PHST- 2019/06/27 00:00 [revised] PHST- 2019/06/28 00:00 [accepted] PHST- 2019/07/03 06:00 [pubmed] PHST- 2019/10/01 06:00 [medline] PHST- 2019/07/03 06:00 [entrez] PHST- 2019/09/01 00:00 [pmc-release] AID - CAS14120 [pii] AID - 10.1111/cas.14120 [doi] PST - ppublish SO - Cancer Sci. 2019 Sep;110(9):2884-2893. doi: 10.1111/cas.14120. Epub 2019 Aug 1.