Optimal Care for Patients with Anaplastic Lymphoma Kinase (ALK)–Positive Non–Small Cell Lung Cancer: A Review on the Role and Utility of ALK Inhibitors

References

• Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7–30. doi:10.3322/caac.2159031912902
   PubMed Web of Science ®Google Scholar
• Pikor LA, Ramnarine VR, Lam S, Lam WL. Genetic alterations defining NSCLC subtypes and their therapeutic implications. Lung Cancer. 2013;82(2):179–189. doi:10.1016/j.lungcan.2013.07.02524011633
   PubMed Web of Science ®Google Scholar
• Petersen I. The morphological and molecular diagnosis of lung cancer. Dtsch Arztebl Int. 2011;108(31–32):525–531. doi:10.3238/arztebl.2011.052521886665
   PubMed Web of Science ®Google Scholar
• Khan M, Lin J, Liao G, et al. ALK inhibitors in the treatment of ALK positive NSCLC. Front Oncol. 2019;8(557). doi:10.3389/fonc.2018.00557.
   PubMed Web of Science ®Google Scholar
• Travis WD, Brambilla E, Noguchi M, et al. International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol. 2011;6(2):244–285. doi:10.1097/JTO.0b013e318206a22121252716
   PubMed Web of Science ®Google Scholar
• Paez JG, Janne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004;304(5676):1497–1500. doi:10.1126/science.109931415118125
   PubMed Web of Science ®Google Scholar
• Midha A, Dearden S, McCormack R. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). Am J Cancer Res. 2015;5(9):2892–2911.26609494
   PubMed Web of Science ®Google Scholar
• Sasaki T, Rodig SJ, Chirieac LR, Janne PA. The biology and treatment of EML4-ALK non-small cell lung cancer. Eur J Cancer. 2010;46(10):1773–1780. doi:10.1016/j.ejca.2010.04.00220418096
   PubMed Web of Science ®Google Scholar
• Xu H, Ma D, Yang G, et al. Sequential therapy according to distinct disease progression patterns in advanced ALK-positive non-small-cell lung cancer after crizotinib treatment. Chin J Cancer Res. 2019;31(2):349–356. doi:10.21147/j.issn.1000-9604.2019.02.0931156305
   PubMed Web of Science ®Google Scholar
• Yang L, Ling Y, Guo L, et al. Detection of ALK translocation in non-small cell lung carcinoma (NSCLC) and its clinicopathological significance using the ventana immunohistochemical staining method: A single-center large-scale investigation of 1504 Chinese Han patients. Chin J Cancer Res. 2016;28(5):495–502. doi:10.21147/j.issn.1000-9604.2016.05.0427877008
   PubMed Web of Science ®Google Scholar
• Verzura M, Batagelj E, Bagnes C, et al. Analysis of EML4-ALK rearrangement in non-small cell lung cancer in Argentina. Ann Diagn Pathol. 2018;34:77–81. doi:10.1016/j.anndiagpath.2018.02.00929661733
   PubMed Web of Science ®Google Scholar
• Solomon B, Lovly C. Anaplastic lymphoma kinase (ALK) fusion oncogene positive non-small cell lung cancer In: Lilenbaum RC, editor. Uptodate. Waltham, MA: UpToDate Accessed 75, 2020.
   Google Scholar
• Chia PL, Mitchell P, Dobrovic A, John T. Prevalence and natural history of ALK positive non-small-cell lung cancer and the clinical impact of targeted therapy with ALK inhibitors. Clin Epidemiol. 2014;6:423–432. doi:10.2147/CLEP.S6971825429239
   PubMed Web of Science ®Google Scholar
• Takahashi T, Sonobe M, Kobayashi M, et al. Clinicopathologic features of non-small-cell lung cancer with EML4-ALK fusion gene. Ann Surg Oncol. 2010;17(3):889–897. doi:10.1245/s10434-009-0808-720183914
   PubMed Web of Science ®Google Scholar
• Inamura K, Takeuchi K, Togashi Y, et al. EML4-ALK fusion is linked to histological characteristics in a subset of lung cancers. J Thorac Oncol. 2008;3(1):13–17. doi:10.1097/JTO.0b013e31815e8b6018166835
   PubMed Web of Science ®Google Scholar
• Bauer TM, Felip E, Solomon BJ, et al. Clinical management of adverse events associated with lorlatinib. Oncologist. 2019;24(8):1103–1110. doi:10.1634/theoncologist.2018-038030890623
   PubMed Web of Science ®Google Scholar
• Patel A, Batra U, Prasad KT, et al. Real world experience of treatment and outcome in ALK-rearranged metastatic nonsmall cell lung cancer: A multicenter study from India. Curr Probl Cancer. 2020;44(3):100571. doi:10.1016/j.currproblcancer.2020.10057132234264
   PubMed Web of Science ®Google Scholar
• Shaw AT, Yeap BY, Mino-Kenudson M, et al. Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J Clin Oncol. 2009;27(26):4247–4253. doi:10.1200/JCO.2009.22.699319667264
   PubMed Web of Science ®Google Scholar
• Morris SW, Kirstein MN, Valentine MB, et al. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-hodgkin’s lymphoma. Science. 1994;263(5151):1281–1284. doi:10.1126/science.81221128122112
   PubMed Web of Science ®Google Scholar
• Shaw A, Engelman J. ALK in lung cancer: past, present, and future. J Clin Oncol. 2013;31(8):1105–1111. doi:10.1200/JCO.2012.44.535323401436
   PubMed Web of Science ®Google Scholar
• Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007;448(7153):561–566. doi:10.1038/nature0594517625570
   PubMed Web of Science ®Google Scholar
• Rikova K, Guo A, Zeng Q, et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell. 2007;131(6):1190–1203. doi:10.1016/j.cell.2007.11.02518083107
   PubMed Web of Science ®Google Scholar
• Gandhi S, Chen H, Zhao Y, Dy GK. First-line treatment of advanced ALK-positive non-small-cell lung cancer. Lung Cancer (Auckl). 2015;6:71–82. doi:10.2147/LCTT.S6349128210152
   PubMedGoogle Scholar
• Weickhardt AJ, Aisner DL, Franklin WA, et al. Diagnostic assays for identification of anaplastic lymphoma kinase-positive non-small cell lung cancer. Cancer. 2013;119(8):1467–1477. doi:10.1002/cncr.2791323280244
   PubMed Web of Science ®Google Scholar
• Ou SHI, Azada M, Hsiang DJ, et al. Next-generation sequencing reveals a novel NSCLC ALK f1174v mutation and confirms ALK G1202R mutation confers high-level resistance to alectinib (CH5424802/RO5424802) in ALK-rearranged NSCLC patients who progressed on crizotinib. J Thorac Oncol. 2014;9(4):549–553. doi:10.1097/JTO.000000000000009424736079
   PubMed Web of Science ®Google Scholar
• Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363(18):1693–1703. doi:10.1056/NEJMoa100644820979469
   PubMed Web of Science ®Google Scholar
• Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013;368(25):2385–2394. doi:10.1056/NEJMoa121488623724913
   PubMed Web of Science ®Google Scholar
• Kazandjian D, Blumenthal GM, Chen H-Y, et al. FDA approval summary: crizotinib for the treatment of metastatic non-small cell lung cancer with anaplastic lymphoma kinase rearrangements. Oncologist. 2014;19(10):e5–11. doi:10.1634/theoncologist.2014-024125170012
   PubMed Web of Science ®Google Scholar
• Solomon BJ, Mok T, Kim DW, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014;371(23):2167–2177. doi:10.1056/NEJMoa140844025470694
   PubMed Web of Science ®Google Scholar
• Chuang JC, Neal JW. Crizotinib as first line therapy for advanced ALK-positive non-small cell lung cancers. Transl Lung Cancer Res. 2015;4(5):639–641. doi:10.3978/j.issn.2218-6751.2015.03.0626629437
   PubMedGoogle Scholar
• Paz-Ares LG, de Marinis F, Dediu M, et al. Paramount: final overall survival results of the phase III study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. J Clin Oncol. 2013;31(23):2895–2902. doi:10.1200/JCO.2012.47.110223835707
   PubMed Web of Science ®Google Scholar
• Rothenstein JM, Chooback N. ALK inhibitors, resistance development, clinical trials. Curr Oncol. 2018;25(Suppl 1):S59–S67. doi:10.3747/co.25.376029910648
   PubMedGoogle Scholar
• Lin J, Riely G, Shaw A. Targeting ALK: precision medicine takes on drug resistance. Cancer Discov. 2017;7(2):137–155. doi:10.1158/2159-8290.CD-16-112328122866
   PubMed Web of Science ®Google Scholar
• Gainor JF, Dardaei L, Yoda S, et al. Molecular mechanisms of resistance to first- and second-generation ALK inhibitors in ALK-rearranged lung cancer. Cancer Discov. 2016;6(10):1118–1133. doi:10.1158/2159-8290.CD-16-059627432227
   PubMed Web of Science ®Google Scholar
• Dagogo-Jack I, Shaw AT. Crizotinib resistance: implications for therapeutic strategies. Ann Oncol. 2016;27 Suppl 3:iii42–iii50. doi:10.1093/annonc/mdw30527573756
   PubMed Web of Science ®Google Scholar
• Camidge DR, Bang YJ, Kwak EL, et al. Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase I study. Lancet Oncol. 2012;13(10):1011–1019. doi:10.1016/S1470-2045(12)70344-322954507
   PubMed Web of Science ®Google Scholar
• Solomon BJ, Cappuzzo F, Felip E, et al. Intracranial efficacy of crizotinib versus chemotherapy in patients with advanced ALK-positive non-small-cell lung cancer: results from profile 1014. J Clin Oncol. 2016;34(24):2858–2865. doi:10.1200/JCO.2015.63.588827022118
   PubMed Web of Science ®Google Scholar
• Costa DB, Shaw AT, Ou SH, et al. Clinical experience with crizotinib in patients with advanced ALK-rearranged non-small-cell lung cancer and brain metastases. J Clin Oncol. 2015;33(17):1881–1888. doi:10.1200/JCO.2014.59.053925624436
   PubMed Web of Science ®Google Scholar
• Toyokawa G, Seto T, Takenoyama M, Ichinose Y. Insights into brain metastasis in patients with ALK+ lung cancer: is the brain truly a sanctuary? Cancer Metastasis Rev. 2015;34(4):797–805. doi:10.1007/s10555-015-9592-y26342831
   PubMed Web of Science ®Google Scholar
• Klempner SJ, Ou SH. Anaplastic lymphoma kinase inhibitors in brain metastases from ALK+ non-small cell lung cancer: hitting the target even in the CNS. Chin Clin Oncol. 2015;4(2):20.26112806
   PubMedGoogle Scholar
• Ou SH. Crizotinib: A novel and first-in-class multitargeted tyrosine kinase inhibitor for the treatment of anaplastic lymphoma kinase rearranged non-small cell lung cancer and beyond. Drug Des Devel Ther. 2011;5:471–485. doi:10.2147/DDDT.S19045
   PubMed Web of Science ®Google Scholar
• Costa DB, Kobayashi S, Pandya SS, et al. CSF concentration of the anaplastic lymphoma kinase inhibitor crizotinib. J Clin Oncol. 2011;29(15):e443–e445. doi:10.1200/JCO.2010.34.131321422405
   PubMed Web of Science ®Google Scholar
• Jain RK, Chen H. Spotlight on brigatinib and its potential in the treatment of patients with metastatic ALK-positive non-small cell lung cancer who are resistant or intolerant to crizotinib. Lung Cancer (Auckl). 2017;8:169–177. doi:10.2147/LCTT.S12650729075144
   PubMed Web of Science ®Google Scholar
• Kaneda H, Okamoto I, Nakagawa K. Rapid response of brain metastasis to crizotinib in a patient with ALK rearrangement-positive non-small-cell lung cancer. J Thorac Oncol. 2013;8(4):e32–e33. doi:10.1097/JTO.0b013e318284377123486271
   PubMed Web of Science ®Google Scholar
• Santarpia M, Daffina MG, D’Aveni A, et al. Spotlight on ceritinib in the treatment of ALK+ NSCLC: design, development and place in therapy. Drug Des Devel Ther. 2017;11:2047–2063. doi:10.2147/DDDT.S113500
   PubMed Web of Science ®Google Scholar
• Friboulet L, Li N, Katayama R, et al. The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer. Cancer Discov. 2014;4(6):662–673. doi:10.1158/2159-8290.CD-13-084624675041
   PubMed Web of Science ®Google Scholar
• Massarelli E, Papadimitrakopoulou V. Ceritinib for the treatment of late-stage (metastatic) non–small cell lung cancer. Clin Cancer Res. 2015;21(4):670–674. doi:10.1158/1078-0432.CCR-14-129125564153
   PubMed Web of Science ®Google Scholar
• Shaw AT, Kim DW, Mehra R, et al. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med. 2014;370(13):1189–1197. doi:10.1056/NEJMoa131110724670165
   PubMed Web of Science ®Google Scholar
• Kim DW, Mehra R, Tan DSW, et al. Activity and safety of ceritinib in patients with ALK-rearranged non-small-cell lung cancer (ASCEND-1): updated results from the multicentre, open-label, phase I trial. Lancet Oncol. 2016;17(4):452–463. doi:10.1016/S1470-2045(15)00614-226973324
   PubMed Web of Science ®Google Scholar
• Mok T, Spigel D, Felip E, et al. ASCEND-2: A single-arm, open-label, multicenter phase ii study of ceritinib in adult patients (pts) with ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC) previously treated with chemotherapy and crizotinib (crz). J Clin Oncol. 2015;33(15_suppl):8059. doi:10.1200/jco.2015.33.15_suppl.8059
   Web of Science ®Google Scholar
• Shaw AT, Kim TM, Crino L, et al. Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): A randomised, controlled, open-label, Phase 3 trial. Lancet Oncol. 2017;18(7):874–886. doi:10.1016/S1470-2045(17)30339-X28602779
   PubMed Web of Science ®Google Scholar
• Soria JC, Tan DSW, Chiari R, et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): A randomised, open-label, phase 3 study. Lancet. 2017;389(10072):917–929. doi:10.1016/S0140-6736(17)30123-X28126333
   PubMed Web of Science ®Google Scholar
• Cho BC, Kim DW, Bearz A, et al. ASCEND-8: A randomized Phase 1 study of ceritinib, 450 mg or 600 mg, taken with a low-fat meal versus 750 mg in fasted state in patients with anaplastic lymphoma kinase (ALK)-rearranged metastatic non-small cell lung cancer (NSCLC). J Thorac Oncol. 2017;12(9):1357–1367. doi:10.1016/j.jtho.2017.07.00528729021
   PubMed Web of Science ®Google Scholar
• Cho BC, Obermannova R, Bearz A, et al. Efficacy and safety of ceritinib (450 mg/d or 600 mg/d) with food versus 750-mg/d fasted in patients with ALK receptor tyrosine kinase (ALK)-positive NSCLC: primary efficacy results from the ASCEND-8 study. J Thorac Oncol. 2019;14(7):1255–1265. doi:10.1016/j.jtho.2019.03.00230851442
   PubMed Web of Science ®Google Scholar
• European Society for Medical Oncology. Ceritinib targets brain metastases in patients with ALK-positive NSCLC. Available from: https://www.esmo.org/oncology-news/Ceritinib-Targets-Brain-Metastases-in-Patients-with-ALK-positive-NSCLC. Accessed 75, 2020.
   Google Scholar
• Chow LQ, Barlesi F, Bertino EM, et al. Results of the ASCEND-7 phase II study evaluating ALK inhibitor (ALKi) ceritinib in patients (pts) with ALK+ non-small cell lung cancer (NSCLC) metastatic to the brain. Ann Oncol. 2019;30(Supplement_5):v602–v603. doi:10.1093/annonc/mdz260
   Google Scholar
• Kinoshita K, Asoh K, Furuichi N, et al. Design and synthesis of a highly selective, orally active and potent anaplastic lymphoma kinase inhibitor (CH5424802). Bioorg Med Chem. 2012;20(3):1271–1280. doi:10.1016/j.bmc.2011.12.02122225917
   PubMed Web of Science ®Google Scholar
• Kodama T, Tsukaguchi T, Yoshida M, Kondoh O, Sakamoto H. Selective ALK inhibitor alectinib with potent antitumor activity in models of crizotinib resistance. Cancer Lett. 2014;351(2):215–221. doi:10.1016/j.canlet.2014.05.02024887559
   PubMed Web of Science ®Google Scholar
• Ou SH, Janne PA, Bartlett CH, et al. Clinical benefit of continuing ALK inhibition with crizotinib beyond initial disease progression in patients with advanced ALK-positive NSCLC. Ann Oncol. 2014;25(2):415–422. doi:10.1093/annonc/mdt57224478318
   PubMed Web of Science ®Google Scholar
• Seto T, Kiura K, Nishio M, et al. CH5424802 (RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (af-001jp study): A single-arm, open-label, phase 1–2 study. Lancet Oncol. 2013;14(7):590–598. doi:10.1016/S1470-2045(13)70142-623639470
   PubMed Web of Science ®Google Scholar
• Tamura T, Kiura K, Seto T, et al. Three-year follow-up of an alectinib phase I/II study in ALK-positive non-small-cell lung cancer: af-001jp. J Clin Oncol. 2017;35(14):1515–1521. doi:10.1200/JCO.2016.70.574928296581
   PubMed Web of Science ®Google Scholar
• Gadgeel SM, Gandhi L, Riely GJ, et al. Safety and activity of alectinib against systemic disease and brain metastases in patients with crizotinib-resistant ALK-rearranged non-small-cell lung cancer (af-002jg): results from the dose-finding portion of a phase 1/2 study. Lancet Oncol. 2014;15(10):1119–1128. doi:10.1016/S1470-2045(14)70362-625153538
   PubMed Web of Science ®Google Scholar
• Ou SH, Ahn JS, De Petris L, et al. Alectinib in crizotinib-refractory ALK-rearranged non-small-cell lung cancer: A phase II global study. J Clin Oncol. 2016;34(7):661–668. doi:10.1200/JCO.2015.63.944326598747
   PubMed Web of Science ®Google Scholar
• Shaw AT, Gandhi L, Gadgeel S, et al. Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: A single-group, multicentre, Phase 2 trial. Lancet Oncol. 2016;17(2):234–242. doi:10.1016/S1470-2045(15)00488-X26708155
   PubMed Web of Science ®Google Scholar
• Hida T, Nokihara H, Kondo M, et al. Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. Lancet. 2017;390(10089):29–39. doi:10.1016/S0140-6736(17)30565-228501140
   PubMed Web of Science ®Google Scholar
• Seto T, Nishio M, Hida T, et al. Final PFS analysis and safety data from the phase III J-ALEX study of alectinib (alc) vs. crizotinib (crz) in ALK-inhibitor naïve ALK-positive non-small cell lung cancer (ALK+ NSCLC). J Clin Oncol. 2019;37(15_suppl):9092. doi:10.1200/JCO.2019.37.15_suppl.9092
   Web of Science ®Google Scholar
• Peters S, Camidge DR, Shaw AT, et al. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med. 2017;377(9):829–838. doi:10.1056/NEJMoa170479528586279
   PubMed Web of Science ®Google Scholar
• Camidge DR, Dziadziuszko R, Peters S, et al. Updated efficacy and safety data and impact of the EML4-ALK fusion variant on the efficacy of alectinib in untreated ALK-positive advanced non-small cell lung cancer in the global phase III ALEX study. J Thorac Oncol. 2019;14(7):1233–1243. doi:10.1016/j.jtho.2019.03.00730902613
   PubMed Web of Science ®Google Scholar
• Gadgeel SM, Shaw AT, Govindan R, et al. Pooled analysis of CNS response to alectinib in two studies of pretreated patients with ALK-positive non-small-cell lung cancer. J Clin Oncol. 2016;34(34):4079–4085. doi:10.1200/JCO.2016.68.463927863201
   PubMed Web of Science ®Google Scholar
• Mok TSK, Shaw AT, Camidge RD, et al. The updated OS and safety data from the randomised, phase III ALEX study of alectinib (alc) versus crizotinib (crz) in untreated advanced ALK+ NSCLC. Ann Oncol. 2019;30(Supplement_5):v607. doi:10.1093/annonc/mdz260.006
   Google Scholar
• Dagogo-Jack I, Rooney M, Lin JJ, et al. Treatment with next-generation ALK inhibitors fuels plasma ALK mutation diversity. Clin Cancer Res. 2019;25(22):6662–6670. doi:10.1158/1078-0432.CCR-19-143631358542
   PubMed Web of Science ®Google Scholar
• Huang WS, Liu S, Zou D, et al. Discovery of brigatinib (ap26113), a phosphine oxide-containing, potent, orally active inhibitor of anaplastic lymphoma kinase. J Med Chem. 2016;59(10):4948–4964. doi:10.1021/acs.jmedchem.6b0030627144831
   PubMed Web of Science ®Google Scholar
• Kim DW, Tiseo M, Ahn MJ, et al. Brigatinib in patients with crizotinib-refractory anaplastic lymphoma kinase-positive non-small-cell lung cancer: A randomized, multicenter phase II trial. J Clin Oncol. 2017;35(22):2490–2498. doi:10.1200/JCO.2016.71.590428475456
   PubMed Web of Science ®Google Scholar
• Uchibori K, Inase N, Araki M, et al. Brigatinib combined with anti-EGFR antibody overcomes osimertinib resistance in EGFR-mutated non-small-cell lung cancer. Nat Commun. 2017;8:14768. doi:10.1038/ncomms1476828287083
   PubMed Web of Science ®Google Scholar
• Zhang S, Anjum R, Squillace R, et al. The potent ALK inhibitor brigatinib (ap26113) overcomes mechanisms of resistance to first- and second-generation ALK inhibitors in preclinical models. Clin Cancer Res. 2016;22(22):5527–5538. doi:10.1158/1078-0432.CCR-16-056927780853
   PubMed Web of Science ®Google Scholar
• 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. Lancet Oncol. 2016;17(12):1683–1696. doi:10.1016/S1470-2045(16)30392-827836716
   PubMed Web of Science ®Google Scholar
• Lin J, Zhu V, Schoenfeld A, et al. Brigatinib in patients with alectinib-refractory ALK-positive NSCLC. J Thorac Oncol. 2018;13(10):1530–1538. doi:10.1016/j.jtho.2018.06.00529935304
   PubMed Web of Science ®Google Scholar
• Kim ES, Ou S-HI, Barlesi F, et al. Phase 2 study of brigatinib in patients (pts) with anaplastic lymphoma kinase (ALK)−positive, advanced non–small cell lung cancer (NSCLC) that progressed on alectinib or ceritinib. J Clin Oncol. 2019;37(15_suppl):TPS9115. doi:10.1200/JCO.2019.37.15_suppl.TPS9115
   Web of Science ®Google Scholar
• Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib versus crizotinib in ALK-positive non-small-cell lung cancer. N Engl J Med. 2018;379(21):2027–2039. doi:10.1056/NEJMoa181017130280657
   PubMed Web of Science ®Google Scholar
• Johnson TW, Richardson PF, Bailey S, et al. Discovery of (10r)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2h-8,4-(m etheno)pyrazolo[4,3-h][2,5,11]-benzoxadiazacyclotetradecine-3-carbonitrile (pf-06463922), a macrocyclic inhibitor of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ros1) with preclinical brain exposure and broad-spectrum potency against ALK-resistant mutations. J Med Chem. 2014;57(11):4720–4744. doi:10.1021/jm500261q24819116
   PubMed Web of Science ®Google Scholar
• Solomon BJ, Besse B, Bauer TM, et al. Lorlatinib in patients with ALK-positive non-small-cell lung cancer: results from a global phase 2 study. Lancet Oncol. 2018;19(12):1654–1667. doi:10.1016/S1470-2045(18)30649-130413378
   PubMed Web of Science ®Google Scholar
• Shaw AT, Felip E, Bauer TM, et al. Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial. Lancet Oncol. 2017;18(12):1590–1599. doi:10.1016/S1470-2045(17)30680-029074098
   PubMed Web of Science ®Google Scholar
• National Comprehensive Cancer Network. Non-small cell lung cancer Guideline. Available from: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed 75, 2020.
   Google Scholar
• Gadgeel SM. Sequencing of ALK inhibitors in ALK+ non-small cell lung cancer. Curr Treat Options Oncol. 2017;18(6):36. doi:10.1007/s11864-017-0479-828534251
   PubMed Web of Science ®Google Scholar
• Crystal A, Shaw A, Sequist L, et al. Patient-derived models of acquired resistance can identify effective drug combinations for cancer. Science. 2014;346(6216):1480–1486. doi:10.1126/science.125472125394791
   PubMed Web of Science ®Google Scholar
• Leighl NB, Page RD, Raymond VM, et al. Clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non-small cell lung cancer. Clin Cancer Res. 2019;25(15):4691–4700. doi:10.1158/1078-0432.CCR-19-062430988079
   PubMed Web of Science ®Google Scholar
• European Society for Medical Oncology. Management of advanced/metastatic NSCLC. Available from: https://www.esmo.org/guidelines/lung-and-chest-tumours/metastatic-non-small-cell-lung-cancer/management-of-advanced-metastatic-nsclc. Accessed 75, 2020.
   Google Scholar
• Shaw A, Solomon B, Besse B, et al. ALK Resistance mutations and efficacy of lorlatinib in advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer. J Clin Oncol. 2019;37(16):1370–1379. doi:10.1200/JCO.18.0223630892989
   PubMed Web of Science ®Google Scholar
• Targeted treatment for ALK positive patients who have previously been treated for non-squamous non-small cell lung cancer. Available from: ClinicalTrials.gov. Accessed 75, 2020.
   Google Scholar
• Horn L, Infante JR, Reckamp KL, et al. Ensartinib (x-396) in ALK-positive non-small cell lung cancer: results from a first-in-human phase I/II, multicenter study. Clin Cancer Res. 2018;24(12):2771–2779. doi:10.1158/1078-0432.CCR-17-239829563138
   PubMed Web of Science ®Google Scholar
• Spigel DR, Reynolds C, Waterhouse D, et al. Phase 1/2 study of the safety and tolerability of nivolumab plus crizotinib for the first-line treatment of anaplastic lymphoma kinase translocation - positive advanced non-small cell lung cancer (CheckMate 370). J Thorac Oncol. 2018;13(5):682–688. doi:10.1016/j.jtho.2018.02.02229518553
   PubMed Web of Science ®Google Scholar
• Crizotinib in treating patients with stage Ib-IIIa non-small cell lung cancer that has been removed by surgery and ALK fusion mutations (an ALCHEMIST treatment trial). Available from: ClinicalTrials.gov. Accessed 75, 2020.
   Google Scholar
• A study comparing adjuvant alectinib versus adjuvant platinum-based chemotherapy in patients with ALK positive non-small cell lung cancer. Available from: ClinicalTrials.gov. Accessed 75, 2020.
   Google Scholar
• Evaluating crizotinib in the neoadjuvant setting in patients with non-small cell lung cancer. Available from: ClinicalTrials.gov. Accessed 75, 2020.
   Google Scholar
• Neoadjuvant therapy in resectable non-small cell lung cancer stages IIIA. Available from: ClinicalTrials.gov. Accessed 75, 2020.
   Google Scholar
• Lovly CM, Iyengar P, Gainor JF. Managing resistance to EFGR- and ALK-targeted therapies. Am Soc Clin Oncol Educ Book. 2017;37:607–618. doi:10.14694/EDBK_17625128561721
   PubMedGoogle Scholar
• Katayama R. Therapeutic strategies and mechanisms of drug resistance in anaplastic lymphoma kinase (ALK)-rearranged lung cancer. Pharmacol Ther. 2017;177:1–8. doi:10.1016/j.pharmthera.2017.02.01528185914
   PubMed Web of Science ®Google Scholar
• Tran PN, Klempner SJ. ALK on my mind: alectinib takes an early lead in managing intracranial disease in non-small cell lung cancer with ALK rearrangements. Ann Transl Med. 2017;5(7):173. doi:10.21037/atm.2017.03.4728480209
   PubMed Web of Science ®Google Scholar
• Bauer T, Shaw A, Johnson M, et al. Brain penetration of lorlatinib: cumulative incidences of CNS and non-CNS progression with lorlatinib in patients with previously treated ALK-positive non-small-cell lung cancer. Target Oncol. 2020;15(1):55–65. doi:10.1007/s11523-020-00702-432060867
   PubMed Web of Science ®Google Scholar
• Recondo G, Mezquita L, Facchinetti F, et al. Diverse resistance mechanisms to the third-generation ALK inhibitor lorlatinib in ALK-rearranged lung cancer. Clin Cancer Res. 2020;26(1):242–255. doi:10.1158/1078-0432.CCR-19-110431585938
   PubMed Web of Science ®Google Scholar
• Wilson FH, Johannessen CM, Piccioni F, et al. A functional landscape of resistance to ALK inhibition in lung cancer. Cancer Cell. 2015;27(3):397–408. doi:10.1016/j.ccell.2015.02.00525759024
   PubMed Web of Science ®Google Scholar
• Lovly CM, McDonald NT, Chen H, et al. Rationale for co-targeting IGF-1R and ALK in ALK fusion-positive lung cancer. Nat Med. 2014;20(9):1027–1034. doi:10.1038/nm.366725173427
   PubMed Web of Science ®Google Scholar