Refined Stratification Based on Baseline Concomitant Mutations and Longitudinal Circulating Tumor DNA Monitoring in Advanced EGFR-Mutant Lung Adenocarcinoma Under Gefitinib Treatment

被引:23
|
作者
Duan, Jianchun [1 ]
Xu, JiaChen [1 ]
Wang, Zhijie [1 ]
Bai, Hua [1 ]
Cheng, Ying [2 ]
An, Tongtong [3 ]
Gao, Hongjun [4 ]
Wang, Kai [5 ]
Zhou, Qing [6 ,7 ]
Hu, Yanping [8 ]
Song, Yong [9 ,10 ]
Ding, Cuimin [11 ]
Peng, Feng [12 ]
Liang, Li [13 ]
Hu, Yi [14 ]
Huang, Cheng [15 ]
Zhou, Caicun [16 ]
Shi, Yuankai [1 ]
Han, Jiefei [1 ]
Wang, Di [1 ]
Tian, Yanhua [1 ]
Yang, Zhenlin [1 ,17 ]
Zhang, Li [18 ]
Chuai, Shaokun [19 ]
Ye, Junyi [19 ]
Zhu, Guanshan [20 ]
Zhao, Junhui [21 ]
Wu, Yi-Long [6 ]
Wang, Jie [1 ]
机构
[1] Chinese Acad Med Sci & Peking Union Med Coll, Canc Hosp, Dept Med Oncol, Natl Canc Ctr,State Key Lab Mol Oncol,Natl Clin R, Beijing, Peoples R China
[2] Jilin Canc Hosp, Jilin Prov Canc Hosp, Div Thorac Oncol, Changchun, Peoples R China
[3] Peking Univ, Sch Oncol, Dept Thorac Med Oncol, Beijing Canc Hosp & Inst, Beijing, Peoples R China
[4] 307Th Hosp Chinese Peoples Liberat Army, Beijing, Peoples R China
[5] Zhejiang Univ, Dept Resp Med, Sch Med, Affiliated Hosp 2, Hangzhou, Peoples R China
[6] Guangdong Prov Peoples Hosp, Guangdong Lung Canc Inst, Guangzhou, Peoples R China
[7] Guangdong Acad Med Sci, Guangzhou, Peoples R China
[8] Hubei Canc Hosp, Dept Oncol, Wuhan, Hubei, Peoples R China
[9] Nanjing Gen Hosp, Nanjing Mil Command, Nanjing, Peoples R China
[10] PLA Bayi Hosp, Nanjing, Peoples R China
[11] Hebei Med Univ, Hosp 4, Dept Resp Med, Wuhan, Hubei, Peoples R China
[12] Sichuan Univ, Sch Med, West China Hosp, Ctr Canc, Chengdu, Peoples R China
[13] Peking Univ Third Hosp, Beijing, Peoples R China
[14] Chinese Peoples Liberat Army Gen Hosp, Beijing, Peoples R China
[15] Fujian Med Univ, Dept Med Oncol, Fujian Prov Canc Hosp, Teaching Hosp,Fujian Univ Tradit Chinese Med,Teac, Fuzhou, Peoples R China
[16] Tongji Univ, Shanghai Pulm Hosp, Shanghai, Peoples R China
[17] Chinese Acad Med Sci & Peking Union Med Coll, Canc Hosp, Natl Canc Ctr, Natl Clin Res Ctr Canc,Dept Thoracic Surg, Beijing, Peoples R China
[18] Sun Yat Sen Univ, Canc Ctr, Guangzhou, Peoples R China
[19] Burning Rock Biotech, Guangzhou, Guangdong, Peoples R China
[20] Amoy Diagnost, Xiamen, Peoples R China
[21] Qinghai Univ, Dept Med Oncol, Affiliated Hosp, Xining, Qinghai, Peoples R China
基金
北京市自然科学基金;
关键词
Lung adenocarcinoma; Epidermal growth factor receptor; Comutations; Refined stratification; ctDNA monitoring; RANDOMIZED PHASE-II; OPEN-LABEL; 1ST-LINE TREATMENT; INTRATUMOR HETEROGENEITY; 19; DEL; CANCER; ERLOTINIB; CHEMOTHERAPY; THERAPY; OSIMERTINIB;
D O I
10.1016/j.jtho.2020.08.020
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Introduction: The optimal treatment for EGFR-mutant lung adenocarcinoma (LUAD) remains challenging because of intratumor heterogeneity. We aimed to explore a refined stratification model based on the integrated analysis of circulating tumor DNA (ctDNA) tracking. Methods: ctDNA was prospectively collected at baseline and at every 8 weeks in patients with advanced treatmentnaive EGFR-mutant LUAD under gefitinib treatment enrolled in a phase 2 trial and analyzed using next-generation sequencing of a 168-gene panel. Results: Three subgroups categorized by baseline comutations-EGFR-sensitizing mutations (59, 32.8%), EGFRsensitizing mutations with tumor suppressor mutations (97, 53.9%), and EGFR-sensitizing mutations with other driver mutations (24, 13.3%)-exhibited distinct progression-free survival (13.2 [11.3-15.2] versus 9.3 [7.6-10.5] versus 4.0 [2.4-9.3] months) and overall survival (32.0 [29.2-41.5] versus 21.7 [19.3-27.0] versus 15.5 [10.5-33.7] months, respectively), providing evidence for initial stratification. A total of 63.7% of the patients achieved week 8 ctDNA clearance, with significant difference noted among the three subgroups (74.5% versus 64.0% versus 29.4%, respectively, p = 0.004, Fisher's exact test). Patients without week 8 ctDNA clearance had worse progression-free survival (clearance versus nonclearance 11.2 [9.9-13.2] versus 7.4 [5.6-9.6] months, p = 0.016, Cox regression], especially in the second subgroup [5.8 (5.6-11.5) months], suggesting the necessity of adaptive stratification during treatment. During follow-up, 56.0% and 20.8% of the patients eventually harbored p.T790M and non-p.T790M mutations, respectively, with a significant difference in non-p.T790M mutations among the three subgroups (7.5% versus 15.7% versus 80.0%, respectively, p < 0.001, Fisher's exact test), giving clues to postline treatment. Conclusions: The patients with baseline comutations and ctDNA nonclearance at first visit might require combined therapy because of the limited survival benefit of EGFR tyrosine kinase inhibitor monotherapy. We proposed a refined stratification mode for the whole-course management of EGFR-mutant LUAD. (C) 2020 Published by Elsevier Inc. on behalf of International Association for the Study of Lung Cancer.
引用
收藏
页码:1857 / 1870
页数:14
相关论文
共 35 条
  • [31] Detection of EGFR mutations in plasma circulating tumour DNA as a selection criterion for first-line gefitinib treatment in patients with advanced lung adenocarcinoma (BENEFIT): a phase 2, single-arm, multicentre clinical trial (vol 6, pg 681, 2018)
    Wang, Z.
    Cheng, Y.
    An, T.
    LANCET RESPIRATORY MEDICINE, 2018, 6 (09): : E50 - E50
  • [32] Predicting osimertinib-treatment outcomes through EGFR mutant-fraction monitoring in the circulating tumor DNA of EGFR T790M-positive patients with non-small cell lung cancer (WJOG8815L)
    Sakai, Kazuko
    Takahama, Takayuki
    Shimokawa, Mototsugu
    Azuma, Koichi
    Takeda, Masayuki
    Kato, Terufumi
    Daga, Haruko
    Okamoto, Isamu
    Akamatsu, Hiroaki
    Teraoka, Shunsuke
    Ono, Akira
    Ohira, Tatsuo
    Yokoyama, Toshihide
    Yamamoto, Nobuyuki
    Nakagawa, Kazuhiko
    Nishio, Kazuto
    MOLECULAR ONCOLOGY, 2021, 15 (01) : 126 - 137
  • [33] Clinical potential of circulating tumor DNA (ctDNA)-based molecular response (MR) and baseline blood-based tumor mutational burden (bTMB) for monitoring response to firstline (1L) chemoimmunotherapy in advanced squamous non-small cell lung cancer (sqNSCLC)
    Ciardiello, F.
    Feng, Z.
    Smith, N. R.
    Andric, Z. G.
    Shell, S.
    Yablonovitch, A.
    Guezel, G.
    Scheuenpflug, J.
    ANNALS OF ONCOLOGY, 2022, 33 (07) : S1050 - S1051
  • [34] Retrospective clinical analysis of circulating tumor DNA (ctDNA)-based molecular response (MR) and baseline blood-based tumor mutational burden (bTMB) for monitoring response in phase 3 trial of bintrafusp alfa vs. pembrolizumab treatment of non-small cell lung cancer (NSCLC)
    Feng, Zheng
    Machl, Andreas
    Wang, Danyi
    Overstreet, Brooke
    Yablonovitch, Arielle
    Scheuenpflug, Juergen
    JOURNAL OF CLINICAL ONCOLOGY, 2023, 41 (16)
  • [35] EGFR mutations based on circulating free DNA (cfDNA) in the subset of Japanese patients (pts) from IPASS (IRESSA Pan ASia Study), a Phase III study of first-line gefitinib (G) vs carboplatin/paclitaxel (C/P) in clinically selected patients with advanced non-small-cell lung cancer (NSCLC)
    Yamamoto, N.
    Ichinose, Y.
    Nishiwaki, Y.
    Ohe, Y.
    Nishio, K.
    Jiang, H.
    Duffield, E.
    Saijo, N.
    Mok, T.
    Fukuoka, M.
    EJC SUPPLEMENTS, 2009, 7 (04): : 10 - 10