• James Chih-Hsin Yang, Myung-Ju Ahn, Dong-Wan Kim, Suresh S Ramalingam, Lecia V Sequist, Wu-Chou Su, Sang-We Kim, Joo-Hang Kim, David Planchard, Enriqueta Felip, Fiona Blackhall, Daniel Haggstrom, Kiyotaka Yoh, Silvia Novello, Kathryn Gold, Tomonori Hirashima, Chia-Chi Lin, Helen Mann, Mireille Cantarini, Serban Ghiorghiu, and Pasi A Jänne.
• James Chih-Hsin Yang and Chia-Chi Lin, National Taiwan University Hospital, Taipei; Wu-Chou Su, National Cheng Kung University Hospital, Tainan, Taiwan, Republic of China; Myung-Ju Ahn, Sungkyunkwan University; Dong-Wan Kim, Seoul National University Hospital; Sang-We Kim, Asan Medical Center, Seoul; Joo-Hang Kim, CHA University, Gyeonggi-do, Republic of Korea; Suresh S. Ramalingam, Emory University School of Medicine, Atlanta, GA; Lecia V. Sequist, Massachusetts General Hospital; Pasi A. Jänne, Dana-Farber Cancer Institute, Boston, MA; David Planchard, Institut Gustave Roussy, Villejuif, France; Enriqueta Felip, Vall d'Hebron University Hospital, Barcelona, Spain; Fiona Blackhall, The Christie Hospital; University of Manchester, Manchester; Helen Mann and Serban Ghiorghiu, AstraZeneca, Cambridge; Mireille Cantarini, AstraZeneca, Macclesfield, United Kingdom; Daniel Haggstrom, Carolinas Healthcare System, Charlotte, NC; Kiyotaka Yoh, National Cancer Center Hospital East, Kashiwa, Chiba; Tomonori Hirashima, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Osaka, Japan; Silvia Novello, University of Turin, Turin, Italy; and Kathryn Gold, University of California San Diego Moores Cancer Center, San Diego, CA.
• J. Clin. Oncol. 2017 Apr 20; 35 (12): 1288-1296.

AbstractPurpose 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.

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