The role of comprehensive analysis with circulating tumor DNA in advanced non-small cell lung cancer patients considered for osimertinib treatment

被引：7

作者：

Sueoka-Aragane, Naoko ^{[1
]}

Nakashima, Chiho ^{[1
]}

Yoshida, Hironori ^{[2
]}

Matsumoto, Naohisa ^{[3
]}

Iwanaga, Kentaro ^{[4
]}

Ebi, Noriyuki ^{[5
]}

Nishiyama, Akihiro ^{[6
]}

Yatera, Kazuhiro ^{[7
]}

Kuyama, Shoichi ^{[8
]}

Fukuda, Minoru ^{[9
]}

Ushijima, Sunao ^{[10
]}

Umeguchi, Hitomi ^{[11
]}

Harada, Daijiro ^{[12
]}

Kashiwabara, Kosuke ^{[13
]}

Suetsugu, Takayuki ^{[14
]}

Fujimoto, Nobukazu ^{[15
]}

Tanaka, Fumihiro ^{[16
]}

Uramoto, Hidetaka ^{[17
]}

Yoshii, Chiharu ^{[18
]}

Nakatomi, Katsumi ^{[19
]}

Koh, Genju ^{[20
]}

Seki, Nobuhiko ^{[21
]}

Aoe, Keisuke ^{[22
]}

Nosaki, Kaname ^{[23
]}

Inoue, Koji ^{[24
]}

Takamori, Ayako ^{[25
]}

Kawaguchi, Atsushi ^{[26
]}

机构：

[1] Saga Univ, Divis Hematol Resp Med & Oncol, Dept Internal Med, Fac Med, Saga, Japan

[2] Kyoto Univ, Grad Sch Med, Dept Resp Med, Kyoto, Japan

[3] Juntendo Univ, Dept Resp Med, Grad Sch Med, Tokyo, Japan

[4] Saga Ken Med Ctr Koseikan, Dept Resp Med, Saga, Japan

[5] Iizuka Hosp, Dept Resp Med, Fukuoka, Japan

[6] Kanazawa Univ, Canc Res Inst, Div Med Oncol, Kanazawa, Ishikawa, Japan

[7] Univ Occupat & Environm Hlth, Dept Resp Med, Fukuoka, Japan

[8] Natl Hosp Org Iwakuni Clin Ctr, Dept Resp Med, Yamaguchi, Japan

[9] Nagasaki Univ Hosp, Dept Resp Med, Nagasaki, Japan

[10] Kumamoto City Hosp, Dept Resp Med, Kumamoto, Japan

[11] Karatsu Red Cross Hosp, Dept Resp Med, Saga, Japan

[12] Natl Hosp Org Shikoku Canc Ctr, Dept Thorac Oncol, Matsuyama, Ehime, Japan

[13] Kumamoto Reg Med Ctr, Dept Resp Med, Kumamoto, Japan

[14] Sendai Med Assoc Hosp, Dept Resp Med, Kagoshima, Japan

[15] Okayama Rosai Hosp, Dept Med Oncol, Okayama, Japan

[16] Univ Occupat & Environm Hlth, Dept Surg 2, Kitakyushu, Fukuoka, Japan

[17] Kanazawa Med Univ, Dept Thorac Surg, Uchinada, Ishikawa, Japan

[18] Univ Occupat & Environm Hlth, Wakamatsu Hosp, Dept Resp Med, Kitakyushu, Fukuoka, Japan

[19] Natl Hosp Org Ureshino Med Ctr, Dept Resp Med, Saga, Japan

[20] Yao Tokushukai Gen Hosp, Dept Med Oncol, Osaka, Japan

[21] Teikyo Univ, Sch Med, Dept Internal Med, Div Med Oncol, Tokyo, Japan

[22] Natl Hosp Org Yamaguchi Ube Med Ctr, Dept Med Oncol & Clin Res, Yamaguchi, Japan

[23] Natl Hosp Org Kyushu Canc Ctr, Dept Thorac Oncol, Fukuoka, Japan

[24] Ehime Prefectural Cent Hosp, Dept Resp Med, Matsuyama, Ehime, Japan

[25] Saga Univ Hosp, Clin Res Ctr, Saga, Japan

[26] Saga Univ, Fac Med, Educ & Res Ctr Community Med, Saga, Japan

来源：

CANCER MEDICINE | 2021年 / 10卷 / 12期

关键词：

molecular diagnosis; mutations; next‐ generation sequencing; non‐ small cell lung cancer; EGFR T790M; RESISTANCE; PLASMA; ADENOCARCINOMA; INHIBITORS; TKI;

D O I：

10.1002/cam4.3929

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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(R)), were treated with osimertinib. Plasma samples were collected before and after treatment. Retrospective comprehensive next-generation sequencing (NGS) of ctDNA was performed with Guardant360(R). 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.

引用

页码：3873 / 3885

页数：13

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