日本語フィールド
著者：○Naoko Sueoka-Aragane, Chiho Nakashima, Hironori Yoshida, Naohisa Matsumoto, Kentaro Iwanaga, Noriyuki Ebi, Akihiro Nishiyama, Kazuhiro Yatera, Shoichi Kuyama, Minoru Fukuda, Sunao Ushijima, Hitomi Umeguchi, Daijiro Harada, Kosuke Kashiwabara, Takayuki Suetsugu, Nobukazu Fujimoto, Fumihiro Tanaka, Hidetaka Uramoto, Chiharu Yoshii, Katsumi Nakatomi, Genju Koh, Nobuhiko Seki, Keisuke Aoe, Kaname Nosaki, Koji Inoue, Ayako Takamori, Atsushi Kawaguchi題名：The role of comprehensive analysis with circulating tumor DNA in advanced non-small cell lung cancer patients considered for osimertinib treatment発表情報：Cancer Med 巻: 10 号: 12 ページ: 3873-3885キーワード：molecular diagnosis; mutations; next-generation sequencing; non-small cell lung cancer概要：Background: EGFR mutations are good predictive markers of efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKI), but whether comprehensive genomic analysis beyond EGFR itself with circulating tumor DNA (ctDNA) adds further predictive or prognostic value has not been clarified.
Methods: Patients with NSCLC who progressed after treatment with EGFR-TKI, and with EGFR T790 M detected by an approved companion diagnostic test (cobas® ), were treated with osimertinib. Plasma samples were collected before and after treatment. Retrospective comprehensive next-generation sequencing (NGS) of ctDNA was performed with Guardant360® . Correlation between relevant mutations in ctDNA prior to treatment and clinical outcomes, as well as mechanisms of acquired resistance, were analyzed.
Results: Among 147 patients tested, 57 patients received osimertinib, with an overall response rate (ORR) of 58%. NGS was successful in 54 of 55 available banked plasma samples; EGFR driver mutations were detected in 43 (80%) and T790 M in 32 (59%). The ORR differed significantly depending on the ratio (T790 M allele fraction [AF])/(sum of variant AF) in ctDNA (p = 0.044). The total number of alterations detected in plasma by NGS was higher in early resistance patients (p = 0.025). T790 M was lost in 32% of patients (6 out of 19) after acquired resistance to osimertinib. One patient with RB1 deletion and copy number gains of EGFR, PIK3CA, and MYC in addition to T790 M, showed rapid progression due to suspected small cell transformation.
Conclusions: NGS of ctDNA could be a promising method for predicting osimertinib efficacy in patients with advanced NSCLC harboring EGFR T790 M.抄録：英語フィールド
Author：○Naoko Sueoka-Aragane, Chiho Nakashima, Hironori Yoshida, Naohisa Matsumoto, Kentaro Iwanaga, Noriyuki Ebi, Akihiro Nishiyama, Kazuhiro Yatera, Shoichi Kuyama, Minoru Fukuda, Sunao Ushijima, Hitomi Umeguchi, Daijiro Harada, Kosuke Kashiwabara, Takayuki Suetsugu, Nobukazu Fujimoto, Fumihiro Tanaka, Hidetaka Uramoto, Chiharu Yoshii, Katsumi Nakatomi, Genju Koh, Nobuhiko Seki, Keisuke Aoe, Kaname Nosaki, Koji Inoue, Ayako Takamori, Atsushi KawaguchiTitle：The role of comprehensive analysis with circulating tumor DNA in advanced non-small cell lung cancer patients considered for osimertinib treatmentAnnouncement information:Cancer Med Vol: 10 Issue: 12 Page: 3873-3885Keyword：molecular diagnosis; mutations; next-generation sequencing; non-small cell lung cancerAn abstract：Background: EGFR mutations are good predictive markers of efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKI), but whether comprehensive genomic analysis beyond EGFR itself with circulating tumor DNA (ctDNA) adds further predictive or prognostic value has not been clarified.
Methods: Patients with NSCLC who progressed after treatment with EGFR-TKI, and with EGFR T790 M detected by an approved companion diagnostic test (cobas® ), were treated with osimertinib. Plasma samples were collected before and after treatment. Retrospective comprehensive next-generation sequencing (NGS) of ctDNA was performed with Guardant360® . Correlation between relevant mutations in ctDNA prior to treatment and clinical outcomes, as well as mechanisms of acquired resistance, were analyzed.
Results: Among 147 patients tested, 57 patients received osimertinib, with an overall response rate (ORR) of 58%. NGS was successful in 54 of 55 available banked plasma samples; EGFR driver mutations were detected in 43 (80%) and T790 M in 32 (59%). The ORR differed significantly depending on the ratio (T790 M allele fraction [AF])/(sum of variant AF) in ctDNA (p = 0.044). The total number of alterations detected in plasma by NGS was higher in early resistance patients (p = 0.025). T790 M was lost in 32% of patients (6 out of 19) after acquired resistance to osimertinib. One patient with RB1 deletion and copy number gains of EGFR, PIK3CA, and MYC in addition to T790 M, showed rapid progression due to suspected small cell transformation.
Conclusions: NGS of ctDNA could be a promising method for predicting osimertinib efficacy in patients with advanced NSCLC harboring EGFR T790 M.