Research Papers:

Does afatinib plus bevacizumab combination therapy induce positive conversion of T790M in previously-negative patients?

Akito Hata _, Nobuyuki Katakami, Reiko Kaji, Toshihide Yokoyama, Toshihiko Kaneda, Motohiro Tamiya, Takako Inoue, Hiromi Kimura, Yukihiro Yano, Daisuke Tamura, Satoshi Morita and Shunichi Negoro

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Oncotarget. 2018; 9:34765-34771. https://doi.org/10.18632/oncotarget.26192

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Akito Hata1, Nobuyuki Katakami1, Reiko Kaji1, Toshihide Yokoyama2, Toshihiko Kaneda2, Motohiro Tamiya3, Takako Inoue3, Hiromi Kimura4, Yukihiro Yano4, Daisuke Tamura5, Satoshi Morita6 and Shunichi Negoro7 on behalf of HANSHIN Oncology Group

1Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan

2Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan

3Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan

4Department of Thoracic Oncology, National Hospital Organization Toneyama National Hospital, Toyonaka, Japan

5Department of Respiratory Medicine, Kobe University Graduate School of Medicine, Kobe, Japan

6Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan

7Department of Medical Oncology, Takarazuka City Hospital, Takarazuka, Japan

Correspondence to:

Akito Hata, email: [email protected]

Keywords: afatinib; bevacizumab; T790M; rebiopsy; osimertinib

Received: August 12, 2018     Accepted: September 13, 2018     Published: October 05, 2018


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.

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