Evolución del tratamiento del cáncer de pulmón no células pequeñas con enfermedad ALK positiva

Diana Laura Páramo González, Yoanna Ivette Flores Vega, Elias Antonio Gracia Medina

Texto completo:

HTML PDF

Resumen

El cáncer de pulmón es la primera causa de muerte por cáncer en el mundo. Durante años, la quimioterapia basada en la administración combinada con dobletes de sales de platino ha sido, el tratamiento de primera opción para la mayoría de los pacientes con cáncer de pulmón de células no pequeñas en estadios avanzados. Investigaciones recientes han identificado la presencia de una serie de alteraciones moleculares y genéticas que definen subgrupos específicos de la enfermedad y que además, pueden ser usadas como dianas de terapias dirigidas. Entre ellas, se ha descrito el reordenamiento genético de la quinasa del linfoma anaplásico, que ha sido reportado en un 3-7 % de los pacientes con cáncer de pulmón de células no pequeñas. A partir de este descubrimiento se generó un rápido desarrollo de moléculas terapéuticas que ha propiciado la existencia de tres generaciones de fármacos inhibidores de la quinasa del linfoma anaplásico, marcándose una nueva etapa en el tratamiento de este tipo de tumores. En este artículo tiene como objetivo hacer una revisión del desarrollo y la evolución de la terapia antiquinasa del linfoma anaplásico para, el tratamiento de pacientes con cáncer de pulmón de células no pequeñas y quinasa del linfoma anaplásico positivos.

Referencias

Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F (2018). Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.fr/today , accessed [28/12/2019].

Molina JR, Yang P, Cassivi S, et al. Non-Small Cell Lung Cancer: Epidemiology, risk factors, treatment and survival. Mayo Clin Proc 2008;83(5):584-94

Scagliotti GV, De Marinis F, Rinaldi M, et al. Phase III randomized trial comparing three platinum-based doublets in advanced non-small cell lung cancer. J Clin Oncol. 2002;20(21):4285-91. https://ascopubs.org/doi/10.1200/JCO.2002.02.068

Villalobos P, Wistuba II. Lung Cancer Biomarkers. Hematol Oncol Clin North Am. 2017; 31: 13–29. https://www.hemonc.theclinics.com/article/S0889-8588(16)30120-4/abstract

Yoshida T, Oya Y, Tanaka K, et al: Differential crizotinib response duration among ALK fusion variants in ALK-positive non–small-cell lung cancer. J Clin Oncol 34:3383-3389, 2016. https://ascopubs.org/doi/full/10.1200/JCO.2015.65.8732

Justin FG, Leila Dardaei, Satoshi Y, 1 , Luc F, Ignaty L, et al. Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in ALK -Rearranged Lung Cancer. 2016 AACR 2018; 6(10); 1118–33

Solomon BJ , Mok T , Kim DW , Wu YL , Nakagawa K , Mekhail T , et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med 2014; 371: 2167 – 77.

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; 263:1281–4. 29

Shiota M, Nakamura S, Ichinohasama R, et al. Anaplastic large cell lymphomas expressing the novel chimeric protein p80NPM/ALK: a distinct clinicopathologic entity. Blood 1995;86:1954–60. 30

Iwahara T, Fujimoto J, Wen D, Cupples R, et al. Molecular characterization of ALK, a receptor tyrosine kinase expressed specifically in the nervous system Oncogene 1997;14:439-49

Pulford K, Morris SW, Turturro F. Anaplastic lymphoma kinase proteins in growth control and cancer.J Cell Physiol. 2004;199:33058

Halberg B and Palmer RH. Mechanistic insight into ALK receptor tyrosine kinase in human cancer biology. Nat Rev Cancer 2013;13:685-700

MacDermontt U, Iafrate AJ, Gray NS,et al. Genomic alterations of anaplastic lymphoma kinase may sensitize tumors to anaplastic lymphoma kinase inhibitors. Cancer Res 2008;68:3389-95

Gridelli C, Peters S, Sgambato A, et al. ALK inhibitors in the treatment of advanced NSCLC. Cancer treat Rev 2014; 40:300-6.

Sasaki T, Rodig SJ, Chirieac LR and Jänne PA. The biology and treatment of EML4-ALK non-small cell lung cancer. Eur J Cancer 2010 ; 46:1773-80

Moss_e YP, Wood A, Maris JM. Inhibition of ALK signaling for cancer therapy. Clin Cancer Res 2009;15:5609–14

Koivunen JP, Mermel C, Zejnullahu K, Murphy C, Lifshits E, Holmes AJ, et al. EML4-ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer. Clin Cancer Res 2008;14:4275–83

Rossi A. Alectinib for ALK-positive non-small-cell lung cancer. Expert review of clinical pharmacology 2016;9:1005-13

Schaefer ES, Baik C. Proactive management strategies for potential gastrointestinal adverse reactions with ceritinib in patients with advanced ALK-positive non-small-cell lung cancer. Cancer management and research 2016;8:33-8

Shaw AT, Yeap BY, Mino-Kenudson M, et al. Clinical features and outcomes of patients with non-small cell lung cancer who harbor EMLA4-ALK. J Clin Oncol 2009;27:4247–53

Chiara Lazzari, Gianluca Spitaleri, Chiara Catania, Massimo Barberis, et al.Targeting ALK in patients with advanced Non-Small Cell Lung Cancer: Biology, diagnostic and Therapeutic options. Critical Rew in Oncol/Hematol 2014; 89: 358-365

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;3:13–7

Inamura K, Takeuchi K, Togashi Y, et al. EML4-ALK lung cancers are characterized by rare other mutations, a TTF-1 cell lineage, an acinar histology and young onset. Mod Pathol 2009;22:508–15

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;115:1723–33.

Selinger CI, Rogers TM, Russell PA, et al. Testing for ALK rearrangement in lung adenocarcinoma: a multicenter comparison of immunohistochemistry and fluorescent in situ hybridization. Mod Pathol 2013; 26:1545-1553

Heuckmann JM, Balke-Want H, Malchers F, et al. Differential protein stability and ALK inhibitor sensitivity of EML4-ALK fusion variants. Clin Cancer Res 2012;1:4682–90

Lindeman NI, Cagle PT, Beasley MB, et al. Molecular testing guideline for selection of lung cancer patients for EGFR y ALK tyrosine kinase inhibitors: guideline from the College of American Pathologist, International Association for the Study of Lung Cancer, and Association for molecular Pathology. Arch Pathol Lab Med 2013; 137: 828

Ignatius Ou SH, Azada M, Hsiang DJ, et al. Next – generation sequencing reveals a Novel NSCLC ALK F1174V mutation and confirm ALK G1202R mutation confer high – level resistance to alectinib in ALK –rearranged NSCLC patients who progressed on crizotinib. J Thorac Oncol 2014; 9: 549

Soda M, Choi YL, Enomoto M, et al: Identification of the transforming EML4- ALK fusion gene in non-small-cell lung cancer. Nature 2007; 448:561-566

Kwak El, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non- small-cell lung cancer. N Engl J Med 2010; 363: 1693-1703

Sai-Hong Ignatius Ou. Further Advances in the management of Anaplastic Lymphoma Kinase – Mutated Non Small – Cell Lung Cancer. JCO 2017; 71: 5904-5909

Gainor JF, Dardaei L, Yoda S, et al: Molecular mechanisms of resistance to first- and second-generation ALK inhibitors in ALK-rearranged lung cancer 2016; Cancer Discov 6:1118-1133

Bayliss R, Choi J, Fennell DA, et al: Molecular mechanisms that underpin EML4-ALK driven cancers and their response to targeted drugs. Cell Mol Life Sci 2016: 73:1209-1224

Ou SI, Lee TK, Young L, et al: Dual occurrence of ALK G1202R solvent front mutation and small cell lung cancer transformation as resistance mechanisms to second generation ALK inhibitors without prior exposure to crizotinib. Pitfall of solely relying on liquid re-biopsy? Lung Cancer 2017; 106:110-114

Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non small cell lung cancer. N Engl J Med 2010;363:1693–703

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 1 study. Lancet Oncol 2012;13:1011–9

Kim D, Ahn M, Yang P, et al. Updated results of a global Phase II study with crizotinib in advanced Alk positive NSCLC. Ann Oncol 2012;23(Suppl 9):ixe402

Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK positive lung cancer. N Engl J Med 2013;25:2385–94

Solomon BJ, Mok T, Kim DW, et al. First line crizotinib versus chemotherapy in ALK – positive lung cancer. N Engl J Med 2014; 371: 2167-2177.

Solomon BJ, Kim DW, Wu YL, Nakagawa K, et al. Final Overall Survival Analysis From a Study Comparing First-Line Crizotinib Versus Chemotherapy in ALK-Mutation-Positive Non–Small-Cell Lung Cancer. J Clin Oncol.2018; 77: 4794 – 4806

Weickhardt AJ, Rothman MS, Salian-Mehta S, et al. rapid onset hypogonadism secondary to crizotinib use in metastatic non small cell lung cancer. Cancer 2012;118:5302–9

Li N, Michellys PY, Kim S, et al. Activity of a potent and selective phase I ALK inhibitor LDK378 in naive and crizotinib resistant preclinical tumor models.[abstract] Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B232.

Marsilje TH, Pei W, Chen B, et al. Synthesis, structure-activity relationships and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor LDK378 currently in phase 1 and 2 clinical trials. J Med Chem 2013; 56:5675-90

Kim DW, Mehra R, Tan DS, 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 1 trial. Lancet Oncol 2016; 17: 452–63

Felip E, Orlov S, Park K, et al. Phase 2 study of ceritinib in ALKi naïve patients (pts) with ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC): whole body responses in the overall pt group and in pts with baseline brain metastases (BM). Ann Oncol 2016; 27 (suppl 6): abstract 1208O

Soria JC, Tan DS, Chiari R, Wu YL, et al. First –line ceritinib versus platinum – based chemotherapy in advanced ALK – rearreaged non- small lung cancer (ASCEND-4): a randomized, open-label, phase 3 study. Lancet Oncol 2017; 17: 30123-30136

Shaw AT, Kim TM, Crio L, Gridelli C, et al. Ceritinib versus chemotherapy in patients with ALK rearranged non – small – cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomized, controlled, open label, phase 3 trial. Lancet Oncol 2017; 18: 874 – 86

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

Ignatius SH, Ahn JS, De Petris L, et al. Alectinib in crizotinib – refractory ALK- Rearranged Non- Small – Cell Lung Cancer: Phase Global Study. JCO 2015; 33: 9443- 9454

Peters S, Camidge DR, Shaw AT, et al. Alectinib vs crizotinib in untreated ALK positive non-small-cell lung cancer. N Engl J Med 2017; 377: 829-838

Camidge DR, Dziadziuszko R, Perters 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;14:1233

Isozaki H, Takigawa N, Kiura K. Mechanisms of aacquired resistance to ALK inhibitors and the rationale for treating ALK-positive lung cancer. Cancers (Basel). 2015;7(2):763–783

Zhang S, Anjum R, Squillace R, et al. The potent ALK inhibitor bri¬gatinib (AP26113) overcomes mechanisms of resistance to first- and second-generation ALK inhibitors in preclinical models. Clin Cancer Res. 2016;22(22):5527–5538

Rivera VM, Wang F, Anjum R, et al. Abstract 1794: AP26113 is a dual ALK/EGFR inhibitor: characterization against EGFR T790M in cell and mouse models of NSCLC. Cancer Res. 2014; 72:1794–1794

Kim DW, Tiseo M, Ahn MJ, et al. Brigatinib in patients with crizotinib – refractory ALK positive non – small – cell lung cancer: a randomized phase II trial. J Clin Oncol 2017; 35: 2490 – 2498

Camidge DR, Tiseo M, Ahn MJ et al. Brigatinib in crizotinib – refractory ALK + NSCLC: central assessment and update from ALTA, a pivotal randomized phase 2 trial (abstract). J Thorac Oncol 2017; 12: 1167 – S1169

Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib vs Crizotinib in ALK-positive Non – Small – Cell Lung Cancer 2018; 379: 2027 – 2039

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 broadspectrum potency against ALK-resistant mutations. J Med Chem 2014; 57: 4720–44

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. Cancer Cell 2015; 28: 70–81

Zou HY, Li Q, Engstrom LD, et al. PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations. Proc Natl Acad Sci USA 2015; 112: 3493–98

Besse B, Solomon BJ, Felip E, et al. Lorlatinib with previously treated ALK+ advanced non – small – cell lung cancer. J Clin Oncol 2018 36 suppl 15 [Abstract 9032]

Farrera R, Mezquita L, Besse B. Progress in the Management of Advanced Thoracic Malignancies in 2017. Thorac Oncol 2018; 13(3): 301- 22

Gainor JF , Shaw AT . Emerging paradigms in the development ofresistance to tyrosine kinase inhibitors in lung cancer . J Clin Oncol 2013; 31 : 3987 – 96

Katayama R, Shaw AT, Khan TM, Mino-Kenudson M. et al. Mechanisms of acquired crizotinib resistance in ALK rearranged lung cancers. Sci Transl Med 2012; 4: 120-117

Gainor JF, Dardaei L, et al. Molecular Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in ALK -Rearranged Lung Cancer. Cancer Discovery2016; 6(10):1118–33

Zhang S , Wang F , Keats J , Zhu X , Ning Y , Wardwell SD , et al. Crizotinib- resistant mutants of EML4–ALK identifi ed through an accelerated mutagenesis screen . Chem Biol Drug Des 2011 ; 78 : 999 – 1005

Katayama R , Friboulet L , Koike S , Lockerman EL , Khan TM , Gainor JF , et al. Two novel ALK mutations mediate acquired resistance to the next-generation ALK inhibitor alectinib . Clin Cancer Res 2014 ; 20 : 5686 – 96

Friboulet L , Li N , Katayama R , Lee CC , Gainor JF , Crystal AS , et al. The ALK inhibitor ceritinib overcomes crizotinib resistance in nonsmall cell lung cancer . Cancer Discov 2014 ; 4 : 662 – 73

Isozaki H, Takigawa N, Kiura K. Mechanisms of acquired resistance to ALK inhibitors and the rationale for treating ALK-positive lung cancer. Cancers (Basel). 2015;7(2):763–783

Fujita S , Masago K , Katakami N , Yatabe Y . Transformation to SCLC after treatment with the ALK inhibitor alectinib. J Thorac Oncol 2016 ; 11 : e67 – 72

Ou SI, Lee TK, Young L, et al: Dual occurrence of ALK G1202R solvent front mutation and small cell lung cancer transformation as resistance mechanisms to second generation ALK inhibitors without prior exposure to crizotinib. Pitfall of solely relying on liquid re-biopsy? Lung Cancer; 2017 106:110-114

National Comprehensive Cancer Network. Non-small cell lung cancer (V1.2019) https://www.nccn.org/professionals/physician_gls/default.aspx#nscl Accessed [28/11/2019].

Diruisseau M, Besse B, Cadranel G, et al. Overall survival with crizotinib and next generation ALK inhibitors in ALK – positive non – small – cell lung cancer (IFCT -1302): A French nationwide cohort retrospective study. Oncotarget 2017;8:21903-21917

Enlaces refback

  • No hay ningún enlace refback.




Copyright (c) 2020 Diana Laura Páramo González, Yoanna Ivette Flores Vega, Elias Antonio Gracia Medina

Licencia de Creative Commons
Esta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial 4.0 Internacional.