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      Switching from first or second generation EGFR-TKI to osimertinib in EGFR mutation-positive NSCLC

      brief-report

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          Abstract

          Aim:

          We evaluated the efficacy of a novel switch protocol for EGFR-TKIs for EGFR mutation-positive NSCLC.

          Materials & methods:

          Clinical records were collected from the patients who had received one of two sequential combination strategies of EGFR-TKIs: Salvage use of osimertinib for T790M-mediated acquired resistance to an prior EGFR-TKI or switch use of osimertinib where an EGFR-TKI was switched to osimertinib before disease progression.

          Results:

          Progression-free survival of osimertinib and time from the start of treatment until progression to osimertinib was comparable between the salvage use and switch use of osimertinib.

          Conclusion:

          Switch use of osimertinib seemed to produce improved efficacy for patients with activating EGFR mutations, because of the lack of patient selection via T790M.

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          Most cited references18

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            Evolution and clinical impact of co-occurring genetic alterations in advanced-stage EGFR-mutant lung cancers

            A widespread approach to modern cancer therapy is to identify a single oncogenic driver gene and target its mutant protein product (e.g. EGFR inhibitor treatment in EGFR-mutant lung cancers). However, genetically-driven resistance to targeted therapy limits patient survival. Through genomic analysis of 1122 EGFR-mutant lung cancer cell-free DNA samples and whole exome analysis of seven longitudinally collected tumor samples from an EGFR-mutant lung cancer patient, we identify critical co-occurring oncogenic events present in most advanced-stage EGFR-mutant lung cancers. We define new pathways limiting EGFR inhibitor response, including WNT/β-catenin and cell cycle gene (e.g. CDK4, CDK6) alterations. Tumor genomic complexity increases with EGFR inhibitor treatment and co-occurring alterations in CTNNB1, and PIK3CA exhibit non-redundant functions that cooperatively promote tumor metastasis or limit EGFR inhibitor response. This study challenges the prevailing single-gene driver oncogene view and links clinical outcomes to co-occurring genetic alterations in advanced-stage EGFR-mutant lung cancer patients.
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              Osimertinib in Pretreated T790M-Positive Advanced Non-Small-Cell Lung Cancer: AURA Study Phase II Extension Component.

              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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                Author and article information

                Journal
                Lung Cancer Manag
                Lung Cancer Manag
                LMT
                Lung Cancer Management
                Future Medicine Ltd (London, UK )
                1758-1966
                1758-1974
                19 March 2020
                June 2020
                19 March 2020
                : 9
                : 2
                : LMT29
                Affiliations
                [1 ]Department of Thoracic Oncology, Osaka International Cancer Institute 3-1-69 Otemae, Chio-ku, Osaka 541-8567, Japan
                [2 ]Department of Biomedical Statistics & Bioinformatics, Kyoto University Graduate School of Medicine 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
                Author notes
                [* ]Author for correspondence: fimam@ 123456d6.dion.ne.jp
                Article
                10.2217/lmt-2020-0005
                7186852
                32346403
                f6d1d878-f530-4a25-988b-90c7ea594a4f
                © 2020 Fumio Imamura

                This work is licensed under the Attribution-NonCommercial-NoDerivatives 4.0 Unported License

                History
                : 07 February 2020
                : 25 February 2020
                : 19 March 2020
                Page count
                Pages: 8
                Categories
                Short Communication

                egfr-tki,egfr mutation,nsclc,osimertinib,switch,time to failure of strategy

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