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

• Published in: Oncotarget Vol. 9; no. 78; pp. 34765 - 34771
• Main Authors: Hata, Akito, Katakami, Nobuyuki, Kaji, Reiko, Yokoyama, Toshihide, Kaneda, Toshihiko, Tamiya, Motohiro, Inoue, Takako, Kimura, Hiromi, Yano, Yukihiro, Tamura, Daisuke, Morita, Satoshi, Negoro, Shunichi
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 05.10.2018
• Subjects: Research Paper; bevacizumab; afatinib; T790M; rebiopsy; osimertinib
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.26192

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.