CHIH-HSIN YANGAhn M.-J.Kim D.-W.Ramalingam S.S.Sequist L.V.Su W.-C.Kim S.-W.Kim J.-H.Planchard D.Felip E.Blackhall F.Haggstrom D.Yoh K.Novello S.Gold K.Hirashima T.Chia-Chi LinMann H.Cantarini M.Ghiorghiu S.Jänne P.A.2020-05-262020-05-2620170732-183Xhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85017605009&doi=10.1200%2fJCO.2016.70.3223&partnerID=40&md5=bd27638088a5206aeadb3016a683a14ehttps://scholars.lib.ntu.edu.tw/handle/123456789/494948Purpose Osimertinib is an irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) selective for both EGFR-TKI sensitizing (EGFRm) and T790M resistance mutations. AURA (NCT01802632) is a phase I/II clinical trial to determine the dose, safety, and efficacy of osimertinib. This article reports the results from the phase II extension component. Patients and Methods Patients with EGFR-TKI-pretreated EGFRm- and T790M-positive advanced non-small-cell lung cancer (NSCLC) received once-daily osimertinib 80 mg. T790M status was confirmed by central testing from a tumor sample taken after the most recent disease progression. Patients with asymptomatic, stable CNS metastases that did not require corticosteroids were allowed to enroll. The primary end point was objective response rate (ORR) by independent radiology assessment. Secondary end points were disease control rate, duration of response, progression-free survival (PFS), and safety. Patient-reported outcomes comprised an exploratory objective. Results In total, 201 patients received treatment, with a median treatment duration of 13.2 months at the time of data cutoff (November 1, 2015). In evaluable patients (n = 198), ORR was 62% (95% CI, 54% to 68%), and the disease control rate was 90% (95% CI, 85 to 94). Median duration of response in 122 responding patients was 15.2 months (95% CI, 11.3 to not calculable). Median PFS was 12.3 months (95% CI, 9.5 to 13.8). The most common possibly causally related adverse events (investigator assessed) were diarrhea (43%; grade $ 3, 1%) and rash (grouped terms; 40%; grade$3, 1%). Interstitial lung disease (grouped terms) was reported in eight patients (4%; grade 1, n = 2; grade 3, n = 3; grade 5, n = 3). Conclusion In patients with EGFRm T790M advanced NSCLC who progress after EGFR-TKI treatment, osimertinib provides a high ORR, encouraging PFS, and durable response. ? 2017 American Society of Clinical Oncology. All rights reserved.[SDGs]SDG3afatinib; bevacizumab; cetuximab; dacomitinib; epidermal growth factor receptor; erlotinib; gefitinib; osimertinib; platinum derivative; antineoplastic agent; EGFR protein, human; epidermal growth factor receptor; osimertinib; piperazine derivative; protein kinase inhibitor; adult; advanced cancer; aged; Article; asthenia; cancer control; cancer growth; cancer patient; cancer therapy; central nervous system metastasis; decreased appetite; diarrhea; drug capsule; drug dose escalation; drug dose reduction; drug efficacy; drug safety; drug tolerability; dry skin; female; human; interstitial lung disease; major clinical study; male; multicenter study; neutrophil count; non small cell lung cancer; open study; overall survival; paronychia; patient-reported outcome; phase 1 clinical trial; phase 2 clinical trial; priority journal; progression free survival; QT prolongation; quality of life; rash; response evaluation criteria in solid tumors; tablet formulation; treatment duration; treatment response; vomiting; antagonists and inhibitors; Carcinoma, Non-Small-Cell Lung; clinical trial; disease free survival; enzymology; genetics; Lung Neoplasms; middle aged; mutation; treatment outcome; very elderly; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Piperazines; Protein Kinase Inhibitors; Receptor, Epidermal Growth Factor; Treatment Outcomejournal article10.1200/JCO.2016.70.3223282218672-s2.0-85017605009