Brigatinib combined with anti-EGFR antibody overcomes osimertinib resistance in EGFR-mutated non-small-cell lung cancer

Nature Communications

Volumn 8, Issue , 2017, Pages

  Uchibori, Ken ^a,b   Inase, Naohiko ^b   Araki, Mitsugu ^c   Kamada, Mayumi ^d   Sato, Shigeo ^a   Okuno, Yasushi ^c,d   Fujita, Naoya ^a   Katayama, Ryohei ^a  

^a CANCER CHEMOTHERAPY CENTER   (Japan)

^b TOKYO MEDICAL AND DENTAL UNIVERSITY   (Japan)

^c RIKEN Center for Computational Science   (Japan)

^d KYOTO UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ANAPLASTIC LYMPHOMA KINASE INHIBITOR; BRIGATINIB; CETUXIMAB; CYSTEINE; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR ANTIBODY; OSIMERTINIB; PROTEIN TYROSINE KINASE INHIBITOR; ANTINEOPLASTIC AGENT; EGFR PROTEIN, HUMAN; MONOCLONAL ANTIBODY; ORGANOPHOSPHORUS COMPOUND; PANITUMUMAB; PIPERAZINE DERIVATIVE; PROTEIN KINASE INHIBITOR; PYRIMIDINE DERIVATIVE;

AMINO ACID; ANATOMY; ANTIBODY; CANCER; CELLS AND CELL COMPONENTS; COMPUTER SIMULATION; DRUG; ENZYME ACTIVITY; GENE EXPRESSION; GROWTH; MUTATION; PROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CHEMICAL STRUCTURE; COMPUTER MODEL; CONTROLLED STUDY; COVALENT BOND; DRUG RESISTANCE; DRUG SCREENING; HUMAN; HUMAN CELL; IC50; LUNG CANCER CELL LINE; MOUSE; MUTATION; NON SMALL CELL LUNG CANCER; NONHUMAN; SIMULATION; STRUCTURE ACTIVITY RELATION; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; DRUG EFFECT; GENE EXPRESSION; GENETICS; LUNG TUMOR; METABOLISM; MOLECULAR DYNAMICS; MORTALITY; NUDE MOUSE; PATHOLOGY; SURVIVAL ANALYSIS; TUMOR CELL LINE; TUMOR VOLUME;

ANIMALS; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CARCINOMA, NON-SMALL-CELL LUNG; CELL LINE, TUMOR; CETUXIMAB; DRUG RESISTANCE, NEOPLASM; GENE EXPRESSION; HUMANS; LUNG NEOPLASMS; MICE; MICE, NUDE; MOLECULAR DYNAMICS SIMULATION; MUTATION; ORGANOPHOSPHORUS COMPOUNDS; PIPERAZINES; PROTEIN KINASE INHIBITORS; PYRIMIDINES; RECEPTOR, EPIDERMAL GROWTH FACTOR; SURVIVAL ANALYSIS; TUMOR BURDEN; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 85015236659     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms14768     Document Type: Article

References (61)

1. Kohno, T., et al. RET fusion gene: translation to personalized lung cancertherapy. Cancer Sci. 104, 1396-1400 (2013).
2. Giaccone, G. Epidermal growth factor receptor inhibitors in the treatment ofnon-small-cell lung cancer. J. Clin. Oncol. 23, 3235-3242 (2005).
3. Maemondo, M., et al. Gefitinib or chemotherapy for non-small-cell lung cancerwith mutated EGFR. N. Engl. J. Med. 362, 2380-2388 (2010).
4. Mok, T. S., et al. Gefitinib or carboplatin-paclitaxel in pulmonaryadenocarcinoma. N. Engl. J. Med. 361, 947-957 (2009).
5. Mitsudomi, T., et al. Gefitinib versus cisplatin plus docetaxel in patients withnon-small-cell lung cancer harbouring mutations of the epidermal growthfactor receptor (WJTOG3405): an open label, randomised phase 3 trial. LancetOncol. 11, 121-128 (2010).
6. Melosky, B. Review of EGFR TKIs in metastatic NSCLC, including ongoingtrials. Front. Oncol. 4, 244 (2014).
7. Gao, G., et al. Epidermal growth factor receptor-tyrosine kinase inhibitortherapy is effective as first-line treatment of advanced non-small-cell lungcancer with mutated EGFR: a meta-analysis from six phase III randomizedcontrolled trials. Int. J. Cancer 131, E822-E829 (2012).
8. Zhou, C., et al. Erlotinib versus chemotherapy as first-line treatment for patientswith advanced EGFR mutation-positive non-small-cell lung cancer(OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3study. Lancet Oncol. 12, 735-742 (2011).
9. Rosell, R., et al. Erlotinib versus standard chemotherapy as first-line treatmentfor European patients with advanced EGFR mutation-positive non-small-celllung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 13, 239-246 (2012).
10. Takano, T., et al. EGFR mutations predict survival benefit from gefitinib inpatients with advanced lung adenocarcinoma: a historical comparison ofpatients treated before and after gefitinib approval in Japan. J. Clin. Oncol. 26, 5589-5595 (2008).
11. Schiller, J. H., et al. Comparison of four chemotherapy regimens for advancednon-small-cell lung cancer. N. Engl. J. Med. 346, 92-98 (2002).
12. Yang, J. C.-H., et al. Afatinib versus cisplatin-based chemotherapy for EGFRmutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6):analysis of overall survival data from two randomised, phase 3 trials. LancetOncol. 16, 141-151 (2015).
13. Hiroshige, Y., et al. Final overall survival results of WJTOG 3405, a randomizedphase 3 trial comparing gefitinib (G) with cisplatin plus docetaxel (CD) as thefirst-line treatment for patients with non-small cell lung cancer (NSCLC)harboring mutations of the epidermal growth factor receptor (EGFR). J. Clin. Oncol. 32, 8117 (2014).
14. Inoue, A., et al. Updated overall survival results from a randomized phase IIItrial comparing gefitinib with carboplatin-paclitaxel for chemo-naive non-smallcell lung cancer with sensitive EGFR gene mutations (NEJ002). Ann. Oncol. 24, 54-59 (2012).
15. Kris, M. G., et al. Using multiplexed assays of oncogenic drivers in lung cancersto select targeted drugs. JAMA 311, 1998-2006 (2014).
16. Kobayashi, S., et al. EGFR mutation and resistance of non-small-cell lung cancerto gefitinib. N. Engl. J. Med. 352, 786-792 (2005).
17. Kosaka, T., et al. Analysis of epidermal growth factor receptor gene mutation inpatients with non-small cell lung cancer and acquired resistance to gefitinib. Clin. Cancer Res. 12, 5764-5769 (2006).
18. Yu, H. A., et al. Analysis of tumor specimens at the time of acquired resistanceto EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers. Clin. Cancer Res. 19, 2240-2247 (2013).
19. Camidge, D. R., Pao, W., Sequist, L. V. Acquired resistance to TKIs insolid tumours: learning from lung cancer. Nat. Rev. Clin. Oncol. 11, 473-481(2014).
20. Sequist, L. V., et al. Neratinib, an irreversible pan-ErbB receptor tyrosine kinaseinhibitor: results of a phase II trial in patients with advanced non-small-celllung cancer. J. Clin. Oncol. 28, 3076-3083 (2010).
21. Sequist, L. V., et al. Activity of IPI-504, a novel heat-shock protein 90 inhibitor, in patients with molecularly defined non-small-cell lung cancer. J. Clin. Oncol. 28, 4953-4960 (2010).
22. Johnson, M. L., et al. Phase II trial of dasatinib for patients with acquiredresistance to treatment with the epidermal growth factor receptor tyrosinekinase inhibitors erlotinib or gefitinib. J. Thorac. Oncol. 6, 1128-1131 (2011).
23. Miller, V. A., et al. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomisedtrial. Lancet Oncol. 13, 528-538 (2012).
24. Riely, G. J., et al. Prospective assessment of discontinuation and reinitiationof erlotinib or gefitinib in patients with acquired resistance to erlotinib orgefitinib followed by the addition of everolimus. Clin. Cancer Res. 13, 5150-5155 (2007).
25. Janjigian, Y. Y., et al. Dual inhibition of EGFR with afatinib and cetuximab inkinase inhibitor-resistant EGFR-mutant lung cancer with and without T790Mmutations. Cancer Discov. 4, 1036-1045 (2014).
26. Zhou, W., et al. Novel mutant-selective EGFR kinase inhibitors against EGFRT790M. Nature 462, 1070-1074 (2009).
27. Cross, D. A., et al. AZD9291, an irreversible EGFR TKI, overcomes T790Mmediatedresistance to EGFR inhibitors in lung cancer. Cancer Discov. 4, 1046-1061 (2014).
28. Walter, A. O., et al. Discovery of a mutant-selective covalent inhibitor of EGFRthat overcomes T790M-mediated resistance in NSCLC. Cancer Discov. 3, 1404-1415 (2013).
29. Janne, P. A., et al. Clinical activity of the mutant-selective EGFR inhibitorAZD9291 in patients (pts) with EGFR inhibitor-resistant non-small cell lungcancer (NSCLC). J. Clin. Oncol. 32, 8009 (2014).
30. Jänne, P. A., et al. AZD9291 in EGFR inhibitor-resistant non-small-cell lungcancer. N. Engl. J. Med. 372, 1689-1699 (2015).
31. Thress, K. S., et al. Acquired EGFR C797S mutation mediates resistance toAZD9291 in non-small cell lung cancer harboring EGFR T790M. Nat. Med. 21, 560-562 (2015).
32. Ercan, D., et al. EGFR mutations and resistance to irreversible pyrimidine-basedEGFR inhibitors. Clin. Cancer Res. 21, 3913-3923 (2015).
33. Kosaka, T., Yamaki, E., Mogi, A., Kuwano, H. Mechanisms of resistance toEGFR TKIs and development of a new generation of drugs in non-small-celllung cancer. J. Biomed. Biotechnol. 2011, 165214 (2011).
34. Stephens, P., et al. Lung cancer: intragenic ERBB2 kinase mutations in tumours. Nature 431, 525-526 (2004).
35. Engelman, J. A., et al. Allelic dilution obscures detection of a biologicallysignificant resistance mutation in EGFR-amplified lung cancer. J. Clin. Invest. 116, 2695-2706 (2006).
36. Engelman, J. A., et al. MET amplification leads to gefitinib resistance in lungcancer by activating ERBB3 signaling. Science 316, 1039-1043 (2007).
37. Yano, S., et al. Hepatocyte growth factor induces gefitinib resistance of lungadenocarcinoma with epidermal growth factor receptor-activating mutations. Cancer Res. 68, 9479-9487 (2008).
38. Ohashi, K., et al. Lung cancers with acquired resistance to EGFR inhibitorsoccasionally harbor BRAF gene mutations but lack mutations in KRAS, NRAS, or MEK1. Proc. Natl Acad. Sci. USA 109, E2127-E2133 (2012).
39. Sequist, L. V., et al. Genotypic and histological evolution of lung cancersacquiring resistance to EGFR inhibitors. Sci. Transl. Med. 3, 75ra26 (2011).
40. Planchard, D., et al. EGFR-independent mechanisms of acquired resistance toAZD9291 in EGFR T790M-positive NSCLC patients. Ann. Oncol. 26, 2073-2078 (2015).
41. Ham, J. S., et al. Two cases of small cell lung cancer transformation from EGFRmutant adenocarcinoma during AZD9291 treatment. J. Thorac. Oncol. 11, e1-e4(2016).
42. Jia, Y., et al. Overcoming EGFR(T790M) and EGFR(C797S) resistance withmutant-selective allosteric inhibitors. Nature 534, 129-132 (2016).
43. Niederst, M. J., et al. The allelic context of the C797S mutation acquired upontreatment with third-generation EGFR inhibitors impacts sensitivity tosubsequent treatment strategies. Clin. Cancer Res. 21, 3924-3933 (2015).
44. Duong-Ly, K. C., et al. Kinase inhibitor profiling reveals unexpectedopportunities to inhibit disease-associated mutant kinases. Cell Rep. 14, 772-781 (2016).
45. Huang, W. S., et al. Discovery of brigatinib (AP26113), a phosphine oxidecontaining, potent, orally active inhibitor of anaplastic lymphoma kinase. J. Med. Chem. 59, 4948-4964 (2016).
46. Katayama, R., et al. Therapeutic strategies to overcome crizotinib resistance innon-small cell lung cancers harboring the fusion oncogene EML4-ALK. Proc. Natl Acad. Sci. USA 108, 7535-7540 (2011).
47. Regales, L., et al. Dual targeting of EGFR can overcome a major drug resistancemutation in mouse models of EGFR mutant lung cancer. J. Clin. Invest. 119, 3000-3010 (2009).
48. Gettinger, S. N., et al. Activity and safety of brigatinib in ALK-rearranged nonsmall-cell lung cancer and other malignancies: a single-arm, open-label, phase1/2 trial. Lancet Oncol. 17, 1683-1696 (2016).
49. Zhang, S., et al. The potent ALK inhibitor brigatinib (AP26113) overcomesmechanisms of resistance to first-and second-generation ALK inhibitors inpreclinical models. Clin. Cancer Res. 22, 5527-5538 (2016).
50. Geoffrey, R. O., et al. Mechanisms of acquired resistance to AZD9291 in EGFRT790M positive lung cancer. J. Thorac. Oncol. 10, S207 (2015).
51. Goto, J., Kataoka, R., Muta, H., Hirayama, N. ASEDock-docking based onalpha spheres and excluded volumes. J. Chem. Inf. Model. 48, 583-590 (2008).
52. Schmidt, M. W., et al. General atomic and molecular electronic structuresystem. J. Comput. Chem. 14, 1347-1363 (1993).
53. Bayly, C. I., Cieplak, P., Cornell, W., Kollman, P. A. A well-behavedelectrostatic potential based method using charge restraints for deriving atomiccharges: the RESP model. J. Phys. Chem. 97, 10269-10280 (1993).
54. Wang, J., Wolf, R. M., Caldwell, J. W., Kollman, P. A., Case, D. A. Development and testing of a general amber force field. J. Comput. Chem. 25, 1157-1174 (2004).
55. Lindorff-Larsen, K., et al. Improved side-chain torsion potentials for the Amberff99SB protein force field. Proteins 78, 1950-1958 (2010).
56. Jorgensen, W. L., Chandrasekhar, J., Madura, J. D., Impey, R. W., Klein, M. L. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 79, 926-935 (1983).
57. Hess, B., Kutzner, C., van der Spoel, D., Lindahl, E. GROMACS 4: algorithmsfor highly efficient, load-balanced, scalable molecular simulation. J. Chem. Theory Comput. 4, 435-447 (2008).
58. Darden, T., York, D., Pedersen, L. Particle mesh Ewald: an Nlog(N) methodfor Ewald sums in large systems. J. Chem. Phys. 98, 10089-10092 (1993).
59. Hess, B., Bekker, H., Berendsen, H. J. C., Fraaije, J. G. E. M. LINCS: a linearconstraint solver for molecular simulations. J. Comput. Chem. 18, 1463-1472 (1997).
60. Bussi, G., Donadio, D., Parrinello, M. Canonical sampling through velocityrescaling. J. Chem. Phys. 126, 014101 (2007).
61. Parrinello, M., Rahman, A. Polymorphic transitions in single crystals: a newmolecular dynamics method. J. Appl. Phys. 52, 7182-7190 (1981).