Yuko Oya1, Tatsuya Yoshida2,3, Kazuhiro Asada4, Tetsuya Oguri5, Naoki Inui6, Sayako Morikawa7, Kentaro Ito8, Tomoki Kimura9, Eiji Kunii10, Takashi Matsui11, Akihito Kubo12, Tatsuo Kato13, Takashi Abe14, Takeshi Tsuda15, Toyoaki Hida1. 1. Department of Thoracic Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan. 2. Department of Thoracic Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan. tatyoshi@ncc.go.jp. 3. Current Address: Department of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. tatyoshi@ncc.go.jp. 4. Department of Respiratory Medicine, Shizuoka General Hospital, Shizuoka, Japan. 5. Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University, Nagoya, Japan. 6. Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. 7. Department of Respiratory Medicine, Fujita Health University School of Medicine, Toyoake, Japan. 8. Respiratory Center, Matsusaka Municipal Hospital, Matsusaka, Japan. 9. Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan. 10. Department of Respiratory Medicine, Nagoya City West Medical Center, Nagoya, Japan. 11. Department of Respiratory Medicine, Seirei Mikatahara General Hospital, Hamamatsu, Japan. 12. Division of Respiratory Medicine and Allergology, Aichi Medical University School of Medicine, Nagakute, Japan. 13. Department of Respiratory Medicine, National Hospital Organization Nagara Medical Center, Gifu, Japan. 14. Department of Respiratory Medicine, Ogaki Municipal Hospital, Ogaki, Japan. 15. Department of Respiratory Medicine, Toyama Prefectural Central Hospital, Toyama, Japan.
Abstract
BACKGROUND: Cell-free DNA (cfDNA) genotyping in plasma using the cobas EGFR Mutation Test v2 (cobas) is the first liquid biopsy as a companion diagnosis to identify the EGFR T790M mutation (T790M) after the failure of treatment of EGFR-tyrosine kinase inhibitors (TKIs) (1st generation, gefitinib [G] and erlotinib [E] and 2nd generation, afatinib [A]). This study investigated the clinical utility of a liquid biopsy for patients who acquired resistance to afatinib. METHODS: We prospectively collected plasma from 51 patients who had acquired resistance to afatinib between April 2015 and November 2016 to evaluate the frequency of T790M by cobas and digital droplet PCR (UMIN000025112). Additionally, we retrospectively reviewed 38 patients who tested by cobas in plasma after G/E failure to compare for T790M detection between A and with G/E. RESULTS: The detection rate of EGFR-driver and T790M in plasma in patients treated with A (A group) as a first-line EGFR-TKI was lower than with G/E followed by A (G/E→A group), although the differences were not significant (EGFR-driver: 41% [A] vs. 67% [G/E→A], P=0.1867; and T790M: 8% [A] vs. 17% [G/E→A], P=0.5798). In first-line setting, the detection rate for EGFR-driver and T790M in plasma by cobas was lower in A group than in G/E group, although there was no significant difference (EGFR-driver: 34% [A] vs. 52% [G/E], P=0.2072; and T790M: 10% [A] vs. 27% [G/E], P=0.1161). CONCLUSION: The detection of EGFR-driver and T790M in plasma by cobas in patients treated with afatinib might be lower than with G/E in a real-world setting.
BACKGROUND: Cell-free DNA (cfDNA) genotyping in plasma using the cobas EGFR Mutation Test v2 (cobas) is the first liquid biopsy as a companion diagnosis to identify the EGFRT790M mutation (T790M) after the failure of treatment of EGFR-tyrosine kinase inhibitors (TKIs) (1st generation, gefitinib [G] and erlotinib [E] and 2nd generation, afatinib [A]). This study investigated the clinical utility of a liquid biopsy for patients who acquired resistance to afatinib. METHODS: We prospectively collected plasma from 51 patients who had acquired resistance to afatinib between April 2015 and November 2016 to evaluate the frequency of T790M by cobas and digital droplet PCR (UMIN000025112). Additionally, we retrospectively reviewed 38 patients who tested by cobas in plasma after G/E failure to compare for T790M detection between A and with G/E. RESULTS: The detection rate of EGFR-driver and T790M in plasma in patients treated with A (A group) as a first-line EGFR-TKI was lower than with G/E followed by A (G/E→A group), although the differences were not significant (EGFR-driver: 41% [A] vs. 67% [G/E→A], P=0.1867; and T790M: 8% [A] vs. 17% [G/E→A], P=0.5798). In first-line setting, the detection rate for EGFR-driver and T790M in plasma by cobas was lower in A group than in G/E group, although there was no significant difference (EGFR-driver: 34% [A] vs. 52% [G/E], P=0.2072; and T790M: 10% [A] vs. 27% [G/E], P=0.1161). CONCLUSION: The detection of EGFR-driver and T790M in plasma by cobas in patients treated with afatinib might be lower than with G/E in a real-world setting.
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