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Revisiones en Cáncer 00041 / http://dx.doi.org/10.20960/revcancer.00041
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Opciones terapéuticas para el cáncer de pulmón con reordenamiento de ALK o ROS1 (+). Primera línea y manejo de la progresión

Enric Carcereny, Marc Cucurull, Pau Guillén

Prepublicado: 2023-11-10
Publicado: 2024-02-09
VOLUMEN 37, NÚM. 4, julio-agosto (2023), PAG. 180-191

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Hace 20 años, el descubrimiento de los mecanismos de adicción oncogénica supuso un cambio de paradigma en el abordaje y en el tratamiento de los pacientes con cáncer de pulmón. Las primeras alteraciones que se descubrieron fueron las mutaciones de EGFR. Su descubrimiento y tratamiento específico con inhibidores tirosina-cinasa (ITQ) consiguieron cambiar la historia natural del cáncer de pulmón. A esta alteración le siguieron muchas otras alteraciones moleculares, como ALK, ROS1, MET, NTKR, BRAF, HER2, KRAS, etc. En todas ellas, cuando se tratan de manera adecuada con fármacos diana, se reproducen los datos de eficacia en tasa de respuesta, en supervivencia libre de progresión y en calidad de vida, e incluso, en algunos estudios, se demuestra un beneficio en supervivencia global. En el caso concreto de los carcinomas de pulmón con reordenamiento de ALK o de ROS1, estos datos se han confirmado en varios estudios, que se detallan en esta revisión. A pesar de todos estos avances, muchos son los retos que quedan en este subgrupo de pacientes, tanto en el diagnóstico como en el tratamiento, tanto de primera línea como a la progresión o el acceso a los fármacos.

Palabras Clave: Reordenamiento de ALK. Reordenamiento de ROS1. Inhibidores de tirosina-cinasa.



Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. Engl J Med 2004;350(21):2129-39.
DOI: 10.1056/NEJMoa040938
Paez JG, Jänne PA, Lee JC, et al. EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy. Science 2004;304(5676):1497-500.
DOI: 10.1126/science.1099314
Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009;361(10):947-57.
DOI: 10.1056/NEJMoa0810699
Mitsudomi T, Morita S, Yatabe Y, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): An open label, randomized phase 3 trial. Lancet Oncol 2010;11(2):121-8.
DOI: 10.1016/S1470-2045(09)70364-X
Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010;362(25):2380-8.
DOI: 10.1056/NEJMoa0909530
Zhou C, Wu YL, Chen G, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): A multicentre, open-label, randomized, phase 3 study. Lancet Oncol 2011;12(8):735-42.
DOI: 10.1016/S1470-2045(11)70184-X
Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): A multicentre, open-label, randomized phase 3 trial. Lancet Oncol 2012;13(3):239-46.
DOI: 10.1016/S1470-2045(11)70393-X
Sequist LV, Yang JC, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 2013;31(27):3327-34.
DOI: 10.1200/JCO.2012.44.2806
Wu YL, Zhou C, Hu CP, et al. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): An open-label, randomized phase 3 trial. Lancet Oncol 2014;15(2):213-22.
DOI: 10.1016/S1470-2045(13)70604-1
Dias-Santagata D, Akhavanfard S, David SS, et al. Rapid targeted mutational analysis of human tumours: A clinical platform to guide personalized cancer medicine. EMBO Mol Med 2010;2(5):146-58.
DOI: 10.1002/emmm.201000070
Rothschild S. Targeted therapies in non-small cell lung cancer-beyond EGFR and ALK. Cancers (Basel) 2015;7(2):930-49.
DOI: 10.3390/cancers7020816
Bullrich F, Morris SW, Hummel M, et al. Nucleophosmin (NPM) gene rearrangements in Ki-1-positive lymphomas. Cancer Res 1994;54(11):2873-7.
Palmer RH, Vernersson E, Grabbe C, et al. Anaplastic lymphoma kinase: signalling in development and disease. Biochem J 2009;420(3):345-61
DOI: 10.1042/BJ20090387
Allouche M. ALK is a novel dependence receptor: Potential implications in development and cancer. Cell Cycle 2007;6(13):1533-8.
DOI: 10.4161/cc.6.13.4433
Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 2007;448:561-6.
DOI: 10.1038/nature05945
Ouyang T, Bai RY, Bassermann F, et al. Identification and characterization of a nuclear interacting partner of anaplasticlymphoma kinase (NIPA). J Biol Chem 2003;278:30028-36.
DOI: 10.1074/jbc.M300883200
Takeuchi K, Choi YL, Soda M, et al. Multiplex reverse transcription-PCR screening for EML4-ALK fusion transcripts. Clin Cancer Res 2008;14:6618-24.
DOI: 10.1158/1078-0432.CCR-08-1018
Weickhardt AJ, Aisner DL, Franklin WA, et al. Diagnostic assays for identification of anaplastic lymphomakinase-positive non-small cell lung cancer. Cancer 2013;119:1467-77.
DOI: 10.1002/cncr.27913
Villaruz LC, Socinski MA, Weiss J. Guidance for clinicians and patients with non-small cell lung cancer in the time of precision medicine. Front Oncol 2023;13:1124167.
DOI: 10.3389/fonc.2023.1124167
Wang R, Pan Y, Li C, et al. The use of quantitative real-time reverse transcriptase PCR for 5’ and 3’ portions of ALK transcripts to detect ALK rearrangements in lung cancers. Clin Cancer Res 2012;18:4725-32.
DOI: 10.1158/1078-0432.CCR-12-0677
Zhang X, Zhang S, Yang X, et al. Fusion of EML4 and ALK is associated with development of lung adenocarcinomas lacking EGFR and KRAS mutations and is correlated with ALK expression. Mol Cancer 2010;9:188.
DOI: 10.1186/1476-4598-9-188
Koh Y, Kim DW, Kim TM, et al. Clinicopathologic characteristics and outcomes of patients with anaplastic lymphoma kinase-positive advanced pulmonary adenocarcinoma: suggestion for an effective screening strategy for these tumors. J Thorac Oncol 2011;6(5):905-12.
DOI: 10.1097/JTO.0b013e3182111461
Rodig SJ, Mino-Kenudson M, et al. Unique clinicopathologic features characterize ALK-rearranged lung adenocarcinoma in the western population. Clin Cancer Res 2009;15(16):5216-23.
DOI: 10.1158/1078-0432.CCR-09-0802
Wong DW, Leung EL, So KK, et al. The EML4-ALK fusion gene is involved in various histologic types of lung cancers from nonsmokers with wild-type EGFR and KRAS. Cancer 2009;115(8):1723-33.
DOI: 10.1002/cncr.24181
Christensen JG, Zou HY, Arango ME, et al. Cytoreductive antitumor activity of PF-2341066, a novel inhibitor of anaplastic lymphoma kinase and c-Met, in experimental models of anaplastic large-cell lymphoma. Mol Cancer Ther 2007;6(12 Pt 1):3314-22.
DOI: 10.1158/1535-7163.MCT-07-0365
Camidge R, 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 1 study. Lancet Oncol 2012;13(10):1011-9.
DOI: 10.1016/S1470-2045(12)70344-3
Kim D-W, Ahn M-J, Shi, et al. Results of a global phase II study with crizotinib in advanced ALK-positive non-small cell lung cancer (NSCLC). J Clin Oncol 2012;30(Supl.):Abstr.7533.
DOI: 10.1200/jco.2012.30.15_suppl.7533
Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med 2013;368(25):2385-94.
DOI: 10.1056/NEJMoa1214886
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):2167-77.
DOI: 10.1056/NEJMoa1408440
Loren CE, Englund C, Grabbe C, et al. A crucial role for the anaplastic lymphoma kinase receptor tyrosine kinase in gut development in Drosophila melanogaster. EMBO Rep 2003; 4(8):781-6.
DOI: 10.1038/sj.embor.embor897
Bazigou E, Apitz H, Johansson J, et al. Anterograde Jelly belly and Alk receptor tyrosine kinase signaling mediates retinal axon targeting in Drosophila. Cell 2007;128(5):961-75.
DOI: 10.1016/j.cell.2007.02.024
Blackhall F, Shaw A, Jänne P, et al. Crizotinib safety profile in elderly and non-elderly patients with advanced ALK+ non-small cell lung cancer. Poster presented at: the European Cancer Congress; Amsterdam, September 27; 2013.
Shaw AT, Kim DW, Mehra R, et al. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med 2014;370(13):1189-97.
DOI: 10.1056/NEJMoa1311107
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):874-86.
DOI: 10.1016/S1470-2045(17)30339-X
Soria JC, Tan DSW, Chiari 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):917-29.
DOI: 10.1016/S0140-6736(17)30123-X
Cho BC, Kim DW, Bearz A, Laurie SA, 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):1357-67.
DOI: 10.1016/j.jtho.2017.07.005
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;15:1119-28.
DOI: 10.1016/S1470-2045(14)70362-6
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):661–8.] y NP28761 [35. 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):234-42.
DOI: 10.1016/S1470-2045(15)00488-X
Hotta K, Hida T, Nokihara H, et al T. Final overall survival analysis from the phase III J-ALEX study of alectinib versus crizotinib in ALK inhibitor-naïve Japanese patients with ALK-positive non-small-cell lung cancer. ESMO Open 2022;7(4):100527.
DOI: 10.1016/j.esmoop.2022.100527
Peters S, Camidge DR, Shaw AT, et al. ALEX Trial Investigators. Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer. N Engl J Med 2017;377(9):829-38.
DOI: 10.1056/NEJMoa1704795
Gadgeel S, Peters S, Mok T, et al. Alectinib versus crizotinib in treatment-naive anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer: CNS efficacy results from the ALEX study. Ann Oncol 2018;29(11):2214-22.
DOI: 10.1093/annonc/mdy405
Zhou C, Kim SW, Reungwetwattana T, et al. Alectinib versus crizotinib in untreated Asian patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer (ALESIA): a randomised phase 3 study. Lancet Respir Med 2019;7(5):437-46.
DOI: 10.1016/S2213-2600(19)30053-0
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):5527-38.
DOI: 10.1158/1078-0432.CCR-16-0569
Kim DW, Tiseo M, Ahn MJ, et al. Brigatinib in Patients with Crizotinib-Refractory Anaplastic Lymphoma KinasePositive Non-Small-Cell Lung Cancer: A Randomized, Multicenter Phase II Trial. J Clin Oncol 2017;35:2490-8.
DOI: 10.1200/JCO.2016.71.5904
Ou SI, Nishio M, Ahn MJ, et al. Efficacy of Brigatinib in Patients With Advanced ALK-Positive NSCLC Who Progressed on Alectinib or Ceritinib: ALK in Lung Cancer Trial of brigAtinib-2 (ALTA-2). J Thorac Oncol 2022;17(12):1404-14.
DOI: 10.1016/j.jtho.2022.08.018
Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib Versus Crizotinib in ALK Inhibitor-Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L Trial. J Thorac Oncol 2021;16(12):2091-108.
DOI: 10.1016/j.jtho.2021.07.035
Yang Y, Zhou J, Zhou J, et al. Efficacy, safety, and biomarker analysis of ensartinib in crizotinib-resistant, ALK-positive non-small-cell lung cancer: a multicentre, phase 2 trial. Lancet Respir Med 2020;8(1):45-53.
DOI: 10.1016/S2213-2600(19)30252-8
Horn L, Wang Z, Wu G, et al. Ensartinib vs Crizotinib for Patients with Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: A Randomized Clinical Trial. JAMA Oncol 2021;7(11):1617-25.
DOI: 10.1001/jamaoncol.2021.3523
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):1654-67.
DOI: 10.1016/S1470-2045(18)30649-1
Shaw AT, Bauer TM, de Marinis F, et al. CROWN Trial Investigators. First-Line Lorlatinib or Crizotinib in Advanced ALK-Positive Lung Cancer. N Engl J Med 2020;383(21):2018-29.
DOI: 10.1056/NEJMoa2027187
Kris MG, Johnson BE, Berry LD, et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA 2014;311:1998-2006.
DOI: 10.1001/jama.2014.3741
Oxnard GR, Binder A, Jänne PA. New targetable oncogenes in non-small-cell lung cancer. J Clin Oncol 2013;31:1097-104.
DOI: 10.1200/JCO.2012.42.9829
Matsushime H, Wang LH, Shibuya M. Human cros- 1 gene homologous to the v-ros sequence of UR2 sarcoma virus encodes for a transmembrane receptor like molecule. Mol Cell Biol 1986;6:30004.
Birchmeier C, Sharma S, Wigler M. Expression and rearrangement of the ROS1 gene in human glioblastoma cells. Proc Natl Acad Sci USA 1987;84(24):9270-4.
DOI: 10.1073/pnas.84.24.9270
Rikova K, Guo A, Zeng Q, et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 2007;131(6):1190-203.
DOI: 10.1016/j.cell.2007.11.025
Takeuchi K, Soda M, Togashi Y, et al. RET, ROS1 and ALK fusions in lung cancer. Nat Med 2012;18(3):378-81.
DOI: 10.1038/nm.2658
Bergethon K, Shaw AT, Ou SH, et al. ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol 2012;30:863-70.
DOI: 10.1200/JCO.2011.35.6345
Davies KD, Le AT, Theodoro MF, et al. Identifying and targetingROS1 gene fusions in non-small cell lung cancer. Clin Cancer Res 2012;18:4570-9.
DOI: 10.1158/1078-0432.CCR-12-0550
Shaw AT, Ou S, Bang YJ, et al. Crizotinib in ROS1-rearrangednon-small-cell lung cancer. N Engl J Med 2014;371(21):1963-71.
DOI: 10.1056/NEJMoa1406766
Mazieres J, Zalcman G, Crino L, et al. Crizotinib therapy for advanced lung adenocarcinoma and a ROS1 rearrangement: Results from the EUROS1 cohort. J Clin Oncol 2015;33:992-9.
DOI: 10.1200/JCO.2014.58.3302

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