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• W2895682392 abstract "// Akito Hata 1 , Nobuyuki Katakami 1 , Reiko Kaji 1 , Toshihide Yokoyama 2 , Toshihiko Kaneda 2 , Motohiro Tamiya 3 , Takako Inoue 3 , Hiromi Kimura 4 , Yukihiro Yano 4 , Daisuke Tamura 5 , Satoshi Morita 6 and Shunichi Negoro 7 on behalf of HANSHIN Oncology Group 1 Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan 2 Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan 3 Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan 4 Department of Thoracic Oncology, National Hospital Organization Toneyama National Hospital, Toyonaka, Japan 5 Department of Respiratory Medicine, Kobe University Graduate School of Medicine, Kobe, Japan 6 Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan 7 Department of Medical Oncology, Takarazuka City Hospital, Takarazuka, Japan Correspondence to: Akito Hata, email: akitohata@hotmail.com Keywords: afatinib; bevacizumab; T790M; rebiopsy; osimertinib Received: August 12, 2018      Accepted: September 13, 2018      Published: October 05, 2018 ABSTRACT Third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are markedly effective for T790M-positive patients. To confer their clinical benefit to more patients, a novel therapy to induce positive conversion in T790M-negative patients may be possible. We retrospectively reviewed medical records of patients who had received rebiopsy after completion of ABC-study: a prospective phase II study of Afatinib plus Bevacizumab Combination (ABC)-therapy after acquired resistance to EGFR-TKI. Between October 2014 and September 2016, 32 eligible patients were enrolled in ABC-study at our institutes. Eighteen patients were T790M-negative and 14 were T790M-positive before ABC-therapy. Rebiopsy was performed on 13 T790M-negative and 5 T790M-positive patients after progression of ABC-therapy. In 8 (62%) of 13 T790M-negative patients, T790M status changed from negative to positive after ABC-therapy. Seven of these 8 patients underwent osimertinib therapy. The response rate and median time to treatment failure were 86% and 12.2 months, respectively. There were no adverse events ≥grade 3, nor any treatment-related deaths. On the other hand, T790M remained positive after ABC-therapy in all 5 previous T790M-positive patients. ABC-therapy could induce positive conversion of T790M even in previously-negative patients. We hypothesize that ABC-therapy could provoke “clonal selection”, which purifies T790M-positive cancer cells in heterogeneous tumors. Further studies are warranted to confirm this phenomena." @default.
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• W2895682392 date "2018-10-05" @default.
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• W2895682392 title "Does afatinib plus bevacizumab combination therapy induce positive conversion of T790M in previously-negative patients?" @default.
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• W2895682392 doi "https://doi.org/10.18632/oncotarget.26192" @default.
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