Osimertinib in Pretreated T790M-Positive Advanced Non–Small-Cell Lung Cancer: AURA Study Phase II Extension Component
Open accessAbstract
Purpose: 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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The T790M mutation is a well-characterized mechanism of acquired resistance to first- and second-generation TKIs, reported to occur in >60% of cases.
“The “gatekeeper” T790M mutation is a well-characterized mechanism of acquired resistance to first- and second-generation TKIs, which has been reported to occur in >60% of cases.”
From Afatinib for the treatment of <i>EGFR</i> mutation-positive NSCLC: A review of clinical findings (2020) · cites this paper as [47]
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- Authors
- Yang, J. C.-H., Ahn, 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., Lin, C.-C., Mann, H., Cantarini, M., Ghiorghiu, S., & Jänne, P. A.
- Affiliations
- Emory University (US)
- 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...
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2017-04-20
- Volume
- 35
- Issue
- 12
- Pages
- 1288-1296
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2591118779
- Cited by
- 571
- References
- 6
- Citations by year
- 2026: 20 · 2025: 33 · 2024: 42 · 2023: 35 · 2022: 69 · 2021: 70 · 2020: 84 · 2019: 81 · 2018: 92 · 2017: 44 · 2016: 1
- FWCI
- 68.09
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- Research Explorer (The University of Manchester) (submittedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- AstraZeneca
- American Society of Clinical Oncology
- Cancer Research UK (20465)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- T790M mutation, EGFR tyrosine kinase inhibitor resistance, advanced non-small cell lung cancer, EGFR-mutant lung cancer, second-line therapy, objective response rate, progression-free survival, interstitial lung disease, diarrhea, rash, central nervous system metastasis, patient-reported outcomes, treatment efficacy and safety
- MeSH terms
- Acrylamides, Adult, Aged, Aged, 80 and over, Aniline Compounds, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Female, Humans, Indoles, Lung Neoplasms, Male, Middle Aged, Mutation, Piperazines, Pyrimidines, Treatment Outcome, Disease-Free Survival, Protein Kinase Inhibitors, ErbB Receptors
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