Selumetinib: A promising pharmacologic approach for KRAS-mutant advanced non-small-cell lung cancer

Future Oncology

Volumn 9, Issue 2, 2013, Pages 167-177

  Metro, Giulio ^a   Chiari, Rita ^a   Baldi, Alice ^a   De Angelis, Verena ^a   Minotti, Vincenzo ^a   Crinò, Lucio ^a  

^a SANTA MARIA DELLA MISERICORDIA HOSPITAL   (Italy)

Author keywords

BRAF; KRAS; MEK; non small cell lung cancer; selumetinib

Indexed keywords

ARRY 142866; DABRAFENIB; DACARBAZINE; DOCETAXEL; ERLOTINIB; GRANULOCYTE COLONY STIMULATING FACTOR; N (2,3 DIHYDROXYPROPOXY) 3,4 DIFLUORO 2 (2 FLUORO 4 IODOANILINO)BENZAMIDE; PEMETREXED; SELUMETINIB; TEMSIROLIMUS; TRAMETINIB; UNCLASSIFIED DRUG;

ACNE; ADVANCED CANCER; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; BILE DUCT CARCINOMA; CANCER CHEMOTHERAPY; CANCER COMBINATION CHEMOTHERAPY; CANCER SURVIVAL; CHEMOTHERAPY INDUCED EMESIS; COLORECTAL CARCINOMA; DIARRHEA; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG ERUPTION; DRUG HALF LIFE; DRUG METABOLISM; DRUG SAFETY; DRUG SPECIFICITY; DRUG TOLERABILITY; ENZYME PHOSPHORYLATION; FATIGUE; HUMAN; IC 50; LIVER CELL CARCINOMA; LUNG NON SMALL CELL CANCER; MAXIMUM PLASMA CONCENTRATION; MELANOMA; NAUSEA; NEUTROPENIA; OVERALL SURVIVAL; PANCREAS CARCINOMA; PERIPHERAL EDEMA; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; THYROID CARCINOMA; TIME TO MAXIMUM PLASMA CONCENTRATION;

ANIMALS; ANTINEOPLASTIC AGENTS; BENZIMIDAZOLES; CARCINOMA, NON-SMALL-CELL LUNG; CLINICAL TRIALS, PHASE I AS TOPIC; CLINICAL TRIALS, PHASE II AS TOPIC; DRUG EVALUATION, PRECLINICAL; GENES, RAS; HUMANS; LUNG NEOPLASMS; MUTATION; PROTEIN KINASE INHIBITORS; TREATMENT OUTCOME;

EID: 84874087383     PISSN: 14796694     EISSN: 17448301     Source Type: Journal    
DOI: 10.2217/fon.12.198     Document Type: Article

References (50)

1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int. J. Cancer 127(12), 2893-2917 (2010).
2. National Cancer Institute. SEER Cancer Statistics Review, 1975-2009 (Vintage 2009 Populations). Howlader N, Noone AM, Krapcho M et al. (Eds). National Cancer Institute, MD, USA (2012).
3. Sangha R, Price J, Butts CA. Adjuvant therapy in non-small cell lung cancer: current and future directions. Oncologist 15(8), 862-872 (2010).
4. Mok TS, Wu YL, Thongprasert S et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N. Engl. J. Med. 361(10), 947-957 (2009).
5. Kwak EL, Bang YJ, Camidge DR et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N. Engl. J. Med. 363(18), 1693-1703 (2010).
6. De Luca A, Maiello MR, D'Alessio A, Pergameno M, Normanno N. The RAS/ RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches. Expert Opin. Ther. Targets 16(Suppl. 2), S17-27 (2012).
7. Vicent S, López-Picazo JM, Toledo G et al. ERK1/2 is activated in non-small-cell lung cancer and associated with advanced tumours. Br. J. Cancer 90(5), 1047-1052 (2004).
8. Sequist LV, Heist RS, Shaw AT et al. Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice. Ann. Oncol. 22(12), 2616-2624 (2011).
9. Paik PK, Arcila ME, Fara M et al. Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. J. Clin. Oncol. 29(15), 2046-2051 (2011).
10. Marchetti A, Felicioni L, Malatesta S et al. Clinical features and outcome of patients with non-small-cell lung cancer harboring BRAF mutations. J. Clin. Oncol. 29(26), 3574-3579 (2011).
11. Rinehart J, Adjei AA, Lorusso PM et al. Multicenter Phase II study of the oral MEK inhibitor, CI1040, in patients with advanced non-small-cell lung, breast, colon, and pancreatic cancer. J. Clin. Oncol. 22(22), 4456-4462 (2004).
12. Haura EB, Ricart AD, Larson TG et al. A Phase II study of PD0325901, an oral MEK inhibitor, in previously treated patients with advanced non-small cell lung cancer. Clin. Cancer Res. 16(8), 2450-2457 (2010).
13. Hainsworth JD, Cebotaru CL, Kanarev V et al. A Phase II, open-label, randomized study to assess the efficacy and safety of AZD6244 (ARRY142886) versus pemetrexed in patients with non-small cell lung cancer who have failed one or two prior chemotherapeutic regimens. J. Thorac. Oncol. 5(10), 1630-1636 (2010).
14. Janne PA, Shaw AT, Pereira JR et al. Selumetinib plus docetaxel for KRASmutant advanced non-small-cell lung cancer: A randomised, multicentre, placebo-controlled, Phase 2 study. Lancet Oncol. 14(1), 38-47 (2013).
15. Flaherty KT, Infante JR, Daud A et al. Combined BRAF and MEK Inhibition in Melanoma with BRAF V600 Mutations. N. Engl. J. Med. 367(18), 1694-1703 (2012).
16. Yeh TC, Marsh V, Bernat BA et al. Biological characterization of ARRY142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor. Clin. Cancer Res. 13(5), 1576-1583 (2007).
17. Davies BR, Logie A, McKay JS et al. AZD6244 (ARRY142886), a potent inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 kinases: mechanism of action in vivo, pharmacokinetic/ pharmacodynamic relationship, and potential for combination in preclinical models. Mol. Cancer Ther. 6(8), 2209-2219 (2007).
18. Haass NK, Sproesser K, Nguyen TK et al. The mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor AZD6244 (ARRY-142886) induces growth arrest in melanoma cells and tumor regression when combined with docetaxel. Clin. Cancer Res. 14(1), 230-239 (2008).
19. Holt SV, Logié A, Odedra R et al. The MEK1/2 inhibitor, selumetinib (AZD6244; ARRY-142886), enhances anti-tumour efficacy when combined with conventional chemotherapeutic agents in human tumour xenograft models. Br. J. Cancer 106(5), 858-866 (2012).
20. Cockerill M, Logie A, Davies BR et al. Combination studies in vitro and in vivo with Gefitinib (Iressa) and the MEK1/2 inhibitor AZD6244 (ARRY142866). Presented at: AACR-NCI-EORTC meeting 2005. Philadelphia, PA, USA, 14-18 November 2005 (Poster A110).
21. Engelman JA, Chen L, Tan X et al. Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat. Med. 14(12), 1351-1356 (2008).
22. Meng J, Dai B, Fang B et al. Combination treatment with MEK and AKT inhibitors is more effective than each drug alone in human non-small cell lung cancer in vitro and in vivo. PLoS One 5(11), e14124 (2010).
23. Takahashi O, Komaki R, Smith PD et al. Combined MEK and VEGFR inhibition in orthotopic human lung cancer models results in enhanced inhibition of tumor angiogenesis, growth, and metastasis. Clin. Cancer Res. 18(6), 1641-1654 (2012).
24. Holt SV, Logie A, Davies BR et al. Enhanced apoptosis and tumor growth suppression elicited by combination of MEK (selumetinib) and mTOR kinase inhibitors (AZD8055). Cancer Res. 72(7), 1804-1813 (2012).
25. Leijen S, Soetekouw PM, Jeffry Evans TR et al. A Phase I, open-label, randomized crossover study to assess the effect of dosing of the MEK1/2 inhibitor Selumetinib (AZD6244; ARRY142866) in the presence and absence of food in patients with advanced solid tumors. Cancer Chemother. Pharmacol. 68(6), 1619-1628 (2011).
26. Adjei AA, Cohen RB, Franklin W et al. Phase I pharmacokinetic and pharmacodynamic study of the oral, small-molecule mitogen-activated protein kinase kinase 1/2 inhibitor AZD6244 (ARRY142886) in patients with advanced cancers. J. Clin. Oncol. 26(13), 2139-2146 (2008).
27. Banerji U, Camidge DR, Verheul HM et al. The first-in-human study of the hydrogen sulfate (Hyd-sulfate) capsule of the MEK1/2 inhibitor AZD6244 (ARRY-142886): A Phase I open-label multicenter trial in patients with advanced cancer. Clin. Cancer Res. 16(5), 1613-1623 (2010).
28. Patel SP, Lazar AJ, Papadopoulos NE et al. Clinical responses to selumetinib (AZD6244; ARRY142886)-based combination therapy stratified by gene mutations in patients with metastatic melanoma. Cancer doi:10.1002/ cncr.27790 (2012) (Epub ahead of print).
29. Kim K, Infante J, Cohen R et al. A Phase I dose-escalation study of selumetinib in combination with docetaxel in patients with advanced solid tumors. Presented at: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics. San Francisco, CA, USA, 12-16 November 2011 (Abstract B225).
30. Fossella FV, DeVore R, Kerr RN et al. Randomized Phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group. J. Clin. Oncol. 18(12), 2354-2362 (2000).
31. Shepherd FA, Dancey J, Ramlau R et al. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J. Clin. Oncol. 18(10), 2095-2103 (2000).
32. Hanna N, Shepherd FA, Fossella FV et al. Randomized Phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J. Clin. Oncol. 22(9), 1589-1597 (2004).
33. Shepherd FA, Rodrigues Pereira J, Ciuleanu T et al. Erlotinib in previously treated non-small-cell lung cancer. N. Engl. J. Med. 353(2), 123-132 (2005).
34. Janne PA, Shaw A, Pereira JR et al. Efficacy and patient-reported outcomes (PROs) with selumetinib (SEL) + docetaxel (DOC) in KRAS mutant advanced non-small cell lung cancer (NSCLC): A randomized Phase II trial. Presented at: 37th ESMO (European Society for Medical Oncology) Congress. Vienna, Austria, 28 September-2 October 2012 (Abstract 1233).
35. Morgillo F, Cascone T, D'Aiuto E et al. Antitumour efficacy of MEK inhibitors in human lung cancer cells and their derivatives with acquired resistance to different tyrosine kinase inhibitors. Br. J. Cancer 105(3), 382-392 (2011).
36. O'Neil BH, Goff LW, Kauh JS et al. Phase II study of the mitogen-activated protein kinase 1/2 inhibitor selumetinib in patients with advanced hepatocellular carcinoma. J. Clin. Oncol. 29(17), 2350-2356 (2011).
37. Bekaii-Saab T, Phelps MA, Li X et al. Multi-institutional Phase II study of selumetinib in patients with metastatic biliary cancers. J. Clin. Oncol. 29(17), 2357-2363 (2011).
38. Hayes DN, Lucas AS, Tanvetyanon T et al. Phase II efficacy and pharmacogenomic study of selumetinib (AZD6244; ARRY142886) in iodine131 refractory papillary thyroid carcinoma with or without follicular elements. Clin. Cancer Res. 18(7), 2056-2065 (2012).
39. Bennouna J, Lang I, Valladares-Ayerbes M et al. A Phase II, open-label, randomised study to assess the efficacy and safety of the MEK1/2 inhibitor AZD6244 (ARRY142886) versus capecitabine monotherapy in patients with colorectal cancer who have failed one or two prior chemotherapeutic regimens. Invest. New Drugs 29(5), 1021-1028 (2011).
40. Bodoky G, Timcheva C, Spigel DR et al. A Phase II open-label randomized study to assess the efficacy and safety of selumetinib (AZD6244 [ARRY142886]) versus capecitabine in patients with advanced or metastatic pancreatic cancer who have failed first-line gemcitabine therapy. Invest. New Drugs 30(3), 1216-1223 (2012).
41. Kirkwood JM, Bastholt L, Robert C et al. Phase II, open-label, randomized trial of the MEK1/2 inhibitor selumetinib as monotherapy versus temozolomide in patients with advanced melanoma. Clin. Cancer Res. 18(2), 555-567 (2012).
42. Balagula Y, Barth Huston K, Busam KJ et al. Dermatologic side effects associated with the MEK1/2 inhibitor selumetinib (AZD6244, ARRY142886). Invest. New Drugs 29(5), 1114-1121 (2011).
43. Baas JM, Krens LL, Guchelaar HJ et al. Recommendations on management of EGFR inhibitor-induced skin toxicity: A systematic review. Cancer Treat. Rev. 38(5), 505-514 (2012).
44. Chen Z, Cheng K, Walton Z et al. A murine lung cancer co-clinical trial identifies genetic modifiers of therapeutic response. Nature 483(7391), 613-617 (2012).
45. Metro G, Duranti S, De Angelis V et al. Clinical impact of presence and type of KRAS mutation in a population of EGFR wild type (WT) advanced non-small cell lung cancer (NSCLC) patients (pts) treated with platinum-based chemotherapy: A retrospective analysis. Presented at: 37th ESMO (European Society for Medical Oncology) Congress. Vienna, Austria, 28 September-2 October 2012 (Abstract 1302).
46. Metro G, Chiari R, Duranti S et al. Impact of specific mutant KRAS on clinical outcome of EGFRTKI-treated advanced non-small cell lung cancer patients with an EGFR wild type genotype. Lung Cancer 78(1), 81-86 (2012).
47. Riely GJ, Brahmer JR, Planchard D et al. A randomized discontinuation Phase II trial of ridaforolimus in non-small cell lung cancer (NSCLC) patients with KRAS mutations. Presented at: 2012 ASCO Annual Meeting. Chicago, IL, USA, 1-5 June 2012 (Abstract 7531).
48. Sunaga N, Shames DS, Girard L et al. Knockdown of oncogenic KRAS in non-small cell lung cancers suppresses tumor growth and sensitizes tumor cells to targeted therapy. Mol. Cancer Ther. 10(2), 336-346 (2011).
49. Meng J, Peng H, Dai B et al. High level of AKT activity is associated with resistance to MEK inhibitor AZD6244 (ARRY142886). Cancer Biol. Ther. 8(21), 2073-2080 (2009).
50. Turke AB, Song Y, Costa C et al. MEK inhibition leads to PI3K/AKT activation by relieving a negative feedback on ERBB receptors. Cancer Res. 72(13), 3228-3237 (2012).