Chinese advanced fusion-dependent lung cancer patients: Molecular spectrum and treatment options using next generation sequencing—A multicenter study (Yangtze River Delta Lung Cancer Cooperation Group-001).
Authors: Wang Wen Xian , Xu Chun-Wei , Li Ziming , Song Zhengbo , Fang Wenfeng , Miao Liyun , Zhu You-Cai , Zhang Shirong , Song Bin-Bin , Shi Xue-Fei , Yu Genhua , Chen Huafei , Rao Chuangzhou , Huang Jianhui , Zhan Ping , Liu Hongbing , Wang Qian , Lv Tang-Feng , Song Yong , Lu Shun ,   Yangtze River Delta Lung Cancer Cooperation Group
Published: June 2021

e21036

Background: Lung cancer with drug receptor protein kinase fusion is regarded as a large class of molecular event, which is called fusion-dependent lung cancer. Fusion-dependent lung cancer accounts for about 10%-15% of non-small cell lung cancer. Therefore, the identification and detection of fusion-dependent lung cancer patients are very important in China. Here we reported a total of 4111 patients with Chinese fusion-dependent lung cancer. Methods: A multicenter study in China was initiated from Dec. 2019, and lung patients have been enrolled as of Dec. 2020. A total of 4111 patients with fusion-dependent were analyzed based on medical records and detailed patient questionnaires. Results: Of this entire cohort, 4111 patients were identified with fusion-dependent, including ALK fusions (2190, 53.27%), ROS1 fusions (894, 21.75%), RET fusions (521, 12.67%), NTRK fusions (128, 3.11%), FGFR fusions (84, 2.04%), NRG1 fusions (41, 1.00%), ERBB2 fusions (55, 1.34%), BRAF fusions (44, 1.07%), MET fusions (34, 0.83%), EGFR fusions (74, 1.80%), Other fusions (46, 1.12%). In ALK fusions, there were 1856 cases (84.75%) of EML4-, including A20(94.64%) and non-A20(5.36%), and other partners STRN-, KIF5B-, HIP1-, KLCl-, successively; In ROS1 fusions, there were 461 cases (51.57%) of CD74-, and other partners EZR-, SDC4-, SLC34A2-, TPM3-, GOPC-, successively; In RET fusions, there were 329 cases (63.15%) of KIF5B-, and other partners CCDC6-, NCOA4-, ERC1-, successively; In NTRK fusions, there were 22 cases (17.19%) of TPM3-NTRK1, and other types ETV6-NTRK3, LMNA-NTRK1, AGTPBP1-NTRK2 successively; In FGFR fusions, there were 40 cases (47.61%) of FGFR3-TACC3, and other types FGFR2-TACC2, ATE1-FGFR2, BAG4-FGFR1, successively; In NRG1 fusions, there were 11 cases (26.83%) of CD74-, and other partners SDC4-, RBPMS-, successively; In MET fusions, there were 9 cases (26.47%) of CD74-, and other partners HLA-DRB1-, KIF5B-, successively; In ERBB2, BRAF and EGFR fusions, the partners were scattered. And 3643 patiens (88.68%) of the detection were used DNA-based NGS, and Others were used RNA-based NGS. Patients with ALK and ROS1 fusions were routinely treated with targeted therapy. Patients with RET, NTRK, FGFR and NRG1 fusions were actively enrolled in the clinical trial. Patients with ERBB2, BRAF, MET and EGFR fusions were only treated with end-line trial target therapy, and they were eager to be included in the corresponding clinical trials. Conclusions: The common fusions of ALK, ROS1, RET are routine standardized treatment is very important. Although fusions are rare, it can not be ignored. Morever, these patients are eager to receive active targeted therapy. DNA+RNA based NGS is not widely used in China, but it is of great value to detect fusions, especially rare fusions, which is the future development trend.