Research progress on targeted treatment in ROS1-positive non-small cell lung cancer

doi:10.3760/cma.j.issn.1673-422X.2019.12.008

Abstract

Abstract: ROS1 fusion gene is a new potential target for molecular targeted therapy of non-small cell lung cancer (NSCLC). In recent years, more and more scholars focus on ROS1 fusion gene. The results of in vitro experiments and clinical research both show that anaplastic lymphoma kinase (ALK) inhibitors have potent anti-tumor activity in ROS1-positive NSCLC patients, but drug resistance is still inevitable. At present, there is no standardized diagnosis and treatment path for ROS1-positive NSCLC. Therefore, further study on the ALK inhibitors of ROS1 is very important, which can provide a new therapeutic idea for targeted treatment and research of NSCLC patients.

Key words: Carcinoma, non-small-cell lung, Molecular targeted therapy, ROS1 fusion gene

Jin Yao, Weng Yiming, Xu Zexi, Peng Min. Research progress on targeted treatment in ROS1-positive non-small cell lung cancer[J]. Journal of International Oncology, 2019, 46(12): 745-749.

References ［34］

［1］	Park S, Ahn BC, Lim SW, et al. Characteristics and outcome of ROS1-positive non-small cell lung cancer patients in routine clinical practice［J］. J Thorac Oncol, 2018, 13(9): 1373-1382. DOI: 10.1016/j.jtho.2018.05.026.
［2］	Kim HR, Lim SM, Kim HJ, et al. The frequency and impact of ROS1 rearrangement on clinical outcomes in never smokers with lung adenocarcinoma［J］. Ann Oncol, 2013, 24(9): 2364-2370. DOI: 10.1093/annonc/mdt220.
［3］	Shaw AT, Ou SH, Bang YJ, et al. Crizotinib in ROS1-rearranged non-small-cell lung cancer［J］. N Engl J Med, 2014, 371(21): 1963-1971. DOI: 10.1056/NEJMoa1406766.
［4］	Liu C, Yu H, Chang J, et al. Crizotinib in Chinese patients with ROS1-rearranged advanced non-small-cell lung cancer in routine clinical practice［J］. Target Oncol, 2019, 14(3): 315-323. DOI: 10.1007/s11523-019-00636-6.
［5］	Katsurada N, Tachihara M, Jimbo N, et al. Successful treatment of ROS1-rearranged lung cancer complicated by hypertrophic pulmonary osteoarthropathy with crizotinib therapy［J］. Intern Med, 2019, 58(10): 1467-1471. DOI: 10.2169/internalmedicine.1982-18.
［6］	Morris TA, Khoo C, Solomon BC. Targeting ROS1 rearrangements in non-small cell lung cancer: crizotinib and newer generation tyrosine kinase inhibitors［J］. Drugs, 2019, 79(12): 1277-1286. DOI: 10.1007/s40265-019-01164-3.
［7］	Créquit P, Ruppert AM, Rozensztajn N, et al. EGFR and KRAS mutation status in non-small-cell lung cancer occurring in HIV-infected patients［J］. Lung Cancer, 2016, 96: 74-77. DOI: 10.1016/j.lungcan.2015.11.021.
［8］	Kerner GS, Koole MJ, Bongaerts AH, et al. Total body metabolic tumor response in ALK positive non-small cell lung cancer patients treated with ALK inhibition［J］. PLoS One, 2016, 11(5): e0149955. DOI: 10.1371/journal.pone.0149955.
［9］	Juan O, Popat S. Crizotinib for ROS1 patients: one small step in bio-marker testing, one giant leap for advanced NSCLC patients［J］. Lung Cancer, 2017, 104: 131-133. DOI: 10.1016/j.lungcan.2016.11.007.
［10］	Mazières J, Zalcman G, Crinò L, et al. Crizotinib therapy for advanced lung adenocarcinoma and a ROS1 rearrangement: results from the EUROS1 cohort［J］. J Clin Oncol, 2015, 33(9): 992-999. DOI: 10.1200/JCO.2014.58.3302.
［11］	Shen L, Lu S. Crizotinib versus pemetrexed-based chemotherapy in patients with advanced ROS1-rearranged non-small cell lung cancer［J］. J Clin Oncol, 2019, 37(15_suppl): 9101. DOI: 10.1200/JCO.2019.37.15_suppl.9101.
［12］	Sebastian Yves Friedrich Michels, Franklin J, Massuti B, et al. Crizotinib in patients with advanced or metastatic ROS1-rearranged lung cancer (EUCROSS): a European phase Ⅱ clinical trial-updated report on progression-free and overall survival［J］. J Clin Oncol, 2019, 37(15_suppl): 9066. DOI: 10.1200/JCO.2019.37.15_suppl.9066.
［13］	Gainor JF, Tseng D, Yoda S, et al. Patterns of metastatic spread and mechanisms of resistance to crizotinib in ROS1-positive non-small-cell lung cancer［J］. JCO Precis Oncol, 2017, 2017. DOI: 10.1200/PO.17.00063.
［14］	Roys A, Chang X, Liu Y, et al. Resistance mechanisms and potent-targeted therapies of ROS1-positive lung cancer［J］. Cancer Chemother Pharmacol, 2019, 84(4): 679-688. DOI: 10.1007/s00280-019-03902-6.
［15］	Muller IB, De Langen AJ, Honeywell RJ, et al. Overcoming crizotinib resistance in ALK-rearranged NSCLC with the second-generation ALK-inhibitor ceritinib［J］. Expert Rev Anticancer Ther, 2016, 16(2): 147-157. DOI: 10.1586/14737140.2016.1131612.
［16］	Gainor JF, Shaw AT. Fast, food and ceritinib in ALK-positive NSCLC［J］. J Thorac Oncol, 2017, 12(9): 1341-1343. DOI: 10.1016/j.jtho.2017.07.012.
［17］	Lim SM, Kim HR, Lee JS, et al. Open-label, multicenter, phase Ⅱ study of ceritinib in patients with non-small-cell lung cancer harboring ROS1 rearrangement［J］. J Clin Oncol, 2017, 35(23): 2613-2618. DOI: 10.1200/JCO.2016.71.3701.
［18］	Drilon A, Barlesi F, De Braud F, et al. Entrectinib in locally advanced or metastatic ROS1 fusion positive non-small cell lung cancer (NSCLC): integrated analysis of ALKA-372-001, STARTRK-1 and STARTRK-2［J］. Ann Oncol, 2019, 30(Supplement_2). DOI: 10.1093/annonc/mdz063.007.
［19］	Ardini E, Menichincheri M, Banfi P, et al. Entrectinib, a Pan-TRK, ROS1, and ALK inhibitor with activity in multiple molecularly defined cancer indications［J］. Mol Cancer Ther, 2016, 15(4): 628-639. DOI: 10.1158/1535-7163.MCT-15-0758.
［20］	Doebele RC, Petez L, Trinh H, et al. Time-to-treatment discontinuation (TTD) and real-world progression-free survival (rwPFS) as endpoints for comparative efficacy analysis between entrectinib trial and crizotinib real-world ROS1 fusion-positive (ROS1+) NSCLC patients［J］. J Clin Oncol, 2019, 37(15_suppl): 9070. DOI: 10.1200/JCO.2019.37.15_suppl.9070.
［21］	Ahn MJ, Cho BC, Siena S, et al. Entrectinib in patients with locally advanced or metastatic ROS1 fusion-positive non-small cell lung cancer (NSCLC)［J］. J Thorac Oncol, 2017, 12(11): S1783. DOI: 10.1016/j.jtho.2017.09.411.
［22］	Davare MA, Vellore NA, Wagner JP, et al. Structural insight into selectivity and resistance profiles of ROS1 tyrosine kinase inhibitors［J］. Proc Natl Acad Sci U S A, 2015, 112(39): E5381-E5390. DOI: 10.1073/pnas.1515281112.
［23］	Gettinger SN, Bazhenova LA, Langer CJ, et al. Activity and safety of brigatinib in ALK-rearranged non-small-cell lung cancer and other malignancies: a single-arm, open-label, phase 1/2 trial［J］. Lancet Oncol, 2016, 17(12): 1683-1696. DOI: 10.1016/S1470-2045(16)30392-8.
［24］	Chong CR, Bahcall M, Capelletti M, et al. Identification of existing drugs that effectively target NTRK1 and ROS1 rearrangements in lung cancer［J］. Clin Cancer Res, 2017, 23(1): 204-213. DOI: 10.1158/1078-0432.CCR-15-1601.
［25］	Drilon A, Somwar R, Wagner JP, et al. A novel crizotinib-resistant solvent-front mutation responsive to cabozantinib therapy in a patient with ROS1-rearranged lung cancer［J］. Clin Cancer Res, 2016, 22(10): 2351-2358. DOI: 10.1158/1078-0432.CCR-15-2013.
［26］	Katayama R, Kobayashi Y, Friboulet L, et al. Cabozantinib overcomes crizotinib resistance in ROS1 fusion-positive cancer［J］. Clin Cancer Res, 2015, 21(1): 166-174. DOI: 10.1158/1078-0432.CCR-14-1385.
［27］	Hellerstedt BA, Vogelzang NJ, Kluger HM, et al. Results of a phase Ⅱ placebo-controlled randomized discontinuation trial of cabozantinib in patients with non-small-cell lung carcinoma［J］. Clin Lung Cancer, 2019, 20(2): 74-81, e1. DOI: 10.1016/j.cllc.2018.10.006.
［28］	Zou HY, Friboulet L, Kodack DP, et al. PF-06463922, an ALK/ROS1 inhibitor, overcomes resistance to first and second generation ALK inhibitors in preclinical models［J］. Cancer Cell, 2015, 28 (1): 70-81. DOI: 10.1016/j.ccell.2015.05.010.
［29］	Solomon B, Shaw A, Ou S, et al. Phase 2 study of lorlatinib in patients with advanced ALK+/ROS1+non-small-cell lung cancer［J］. J Thorac Oncol, 2017, 12(11): S1756. DOI: 10.1016/j.jtho.2017.09.351.
［30］	Ou S, Shaw A, Rielyet G, et al. Clinical activity of lorlatinib in patients with ROS1+ advanced non-small cell lung cancer: phase 2 study cohort EXP-6［J］. J Thorac Oncol, 2018, 13(10): S322-S323. DOI: 10.1016/j.jtho.2018.08.241.
［31］	Cui JJ, Zhai D, Deng W, et al. TPX-0005, a novel ALK/ROS1/TRK inhibitor, effectively inhibited a broad spectrum of mutations including solvent front ALK G1202R, ROS1 G2032R and TRKA G595R mutants［J］. Eur J Cancer, 2016, 69(Supplement 1): S32. DOI: 10.1016/S0959-8049(16)32675-2.
［32］	Cui JJ, Zhai D, Deng W, et al. Abstract B185: TPX-0005, a supreme ROS1 inhibitor, overcomes crizotinib-resistant ROS1 mutations including solvent front mutation G2032R and gatekeeper mutation L2026M［J］. Mol Cancer Ther, 2018, 17(1_suppl): B185. DOI: 10.1158/1535-7163.TARG-17-B185.
［33］	Drilon AE, Kim DW, Lee J, et al. A phase 1 study of the next-generation ALK/ROS1/TRK inhibitor ropotrectinib (TPX-0005) in patients with advanced ALK/ROS1/NTRK+ cancers (TRIDENT-1)［J］. J Clin Oncol, 2018, 36(15_suppl): 2513. DOI: 10.1200/JCO.2018.36.15_suppl.2513.
［34］	Drilon A, Ou SI, Cho BC, et al. Repotrectinib (TPX-0005) is a next-generation ROS1/TRK/ALK inhibitor that potently inhibits ROS1/TRK/ALK solvent- front mutations［J］. Cancer Discov, 2018, 8(10): 1227-1236. DOI: 10.1158/2159-8290.CD-18-0484.

[1]	Wang Ying, Liu Nan, Guo Bing. Advances of antibody-drug conjugate in the therapy of metastatic breast cancer [J]. Journal of International Oncology, 2024, 51(6): 364-369.
[2]	Wang Peixin, Zhao Jun, Xu Shihong, Jiang Zhaoyang, Wang Xiaoqiang, Yang Hongjuan. Progress of ferroptosis-related mechanisms in osteosarcoma [J]. Journal of International Oncology, 2024, 51(5): 308-311.
[3]	Yang Zhi, Lu Yiqiao, Gu Huayan, Ding Jialing, Guo Guilong. Research progress of tumor microenvironment mediated drug resistance in targeted therapy of breast cancer [J]. Journal of International Oncology, 2024, 51(4): 235-238.
[4]	Huang Hui, Ding Jianghua. Advances in targeting FGFR2 for treatment of advanced cholangiocarcinoma [J]. Journal of International Oncology, 2023, 50(9): 569-573.
[5]	Li Qingshan, Xie Xin, Zhang Nan, Liu Shuai. Research progress on the application of combining radiotherapy and systemic therapy in breast cancer [J]. Journal of International Oncology, 2023, 50(6): 362-367.
[6]	Liu Li, Zhu Siqi, Sun Mengying, He Jingdong. Progress of PARP inhibitors in targeted therapy of small cell lung cancer [J]. Journal of International Oncology, 2023, 50(6): 368-372.
[7]	Liu Bohan, Huang Junxing. Research progress of solute carriers related genes in malignant tumors [J]. Journal of International Oncology, 2023, 50(5): 280-284.
[8]	Zhu Jun, Huang Meijin, Li Yuan, Liu Zegang, Xun Xin, Chen Hong. Research progress on targeted therapy of breast cancer with low expression of HER2 [J]. Journal of International Oncology, 2023, 50(4): 236-240.
[9]	Deng Lili, Duan Xingyu, Li Baozhong. Advances of anti-HER2 targeted drugs and combined therapeutic regimens for gastric and esophagogastic adenocarcinoma [J]. Journal of International Oncology, 2023, 50(12): 751-757.
[10]	Liu Shaoping, Luo Hanchuan, Lin Shuhan, Luo Jiahui. Current status and research progress of interventional and systemic therapy for advanced hepatocellular carcinoma [J]. Journal of International Oncology, 2023, 50(12): 758-762.
[11]	Jiang Shan, Xu Ximing. Recent progresses of targeted therapy and immunotherapy of hepatocellular carcinoma [J]. Journal of International Oncology, 2023, 50(11): 688-695.
[12]	Jiang Shan, Xu Yangtao, Liu Xin, Chen Wenliang, Xu Ximing. Predictive value of baseline peripheral blood inflammatory biomarkers for prognosis in patients with advanced hepatocellular carcinoma treated with immunotherapy combined with targeted therapy [J]. Journal of International Oncology, 2023, 50(10): 600-607.
[13]	Zhang Jingxian, Su Jianfei, Wei Xueqin, Yi Dan, Li Xiaojiang. Treatment status of non-small cell lung cancer with METexon14 skipping mutation [J]. Journal of International Oncology, 2023, 50(1): 37-41.
[14]	Song Jia, Hu Qinyong. Application of TACE combined with molecular targeted therapy and immunotherapy in BCLC B/C hepatocellular carcinoma [J]. Journal of International Oncology, 2022, 49(9): 550-554.
[15]	Zhang Jingxian, Yi Dan, Li Xiaojiang. Application of antibody-drug conjugates in the treatment of non-small cell lung cancer [J]. Journal of International Oncology, 2022, 49(5): 296-301.