A randomized phase II study of the MEK1/MEK2 inhibitor trametinib (GSK1120212) compared with docetaxel in KRAS-mutant advanced non-small-cell lung cancer (NSCLC)

Annals of Oncology

Volumn 26, Issue 5, 2015, Pages 894-901

  Blumenschein, George R ^a   Smit, E F ^b   Planchard, D ^c   Kim, D W ^d   Cadranel, J ^e   De Pas, T ^f   Dunphy, F ^g   Udud, K ^h   Ahn, M J ⁱ   Hanna, N H ^j   Kim, J H ^k   Mazieres, J ^l   Kim, S W ^m   Baas, P ⁿ   Rappold, E ^o   Redhu, S ^o   Puski, A ^p   Wu, F S ^o   Janne P A ^q  

^a UNIVERSITY OF TEXAS   (United States)

^b VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^c INSTITUT GUSTAVE ROUSSY   (France)

^d Seoul National University Hospital   (South Korea)

^e ASSISTANCE PUBLIQUE HÔPITAUX DE PARIS   (France)

^f EUROPEAN INSTITUTE OF ONCOLOGY   (Italy)

^g DUKE UNIVERSITY MEDICAL CENTER   (United States)

^h NATIONAL KORANYI INSTITUTE OF PULMONOLOGY   (Hungary)

ⁱ Sungkyunkwan University School of Medicine   (South Korea)

^j INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^k Yonsei University College of Medicine   (South Korea)

^l TOULOUSE UNIVERSITY HOSPITAL   (France)

^m University of Ulsan College of Medicine   (South Korea)

ⁿ NETHERLANDS CANCER INSTITUTE   (Netherlands)

^o GLAXOSMITHKLINE   (United States)

^p GLAXOSMITHKLINE   (United Kingdom)

^q DANA FARBER CANCER INSTITUTE   (United States)

more..

Author keywords

Docetaxel; KRAS; MEK inhibitor; NSCLC; Progression free survival; Trametinib

Indexed keywords

DOCETAXEL; TRAMETINIB; ANTINEOPLASTIC AGENT; KRAS PROTEIN, HUMAN; MAP2K1 PROTEIN, HUMAN; MAP2K2 PROTEIN, HUMAN; MITOGEN ACTIVATED PROTEIN KINASE KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE KINASE 2; PROTEIN KINASE INHIBITOR; PROTEIN P21; PYRIDONE DERIVATIVE; PYRIMIDINONE DERIVATIVE; TAXOID; TUMOR MARKER;

ACNE; ADULT; AGED; ALOPECIA; ARTICLE; ASTHENIA; CANCER SURVIVAL; CONTROLLED STUDY; COUGHING; CROSSOVER PROCEDURE; DECREASED APPETITE; DIARRHEA; DRUG BLOOD LEVEL; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG RESPONSE; DRUG SAFETY; DRUG WITHDRAWAL; DRY SKIN; DYSGEUSIA; DYSPNEA; FATIGUE; FEMALE; HEART EJECTION FRACTION; HUMAN; HYPERTENSION; LUNG EMBOLISM; MAJOR CLINICAL STUDY; MALE; MUCOSA INFLAMMATION; MULTICENTER STUDY; MYALGIA; NAUSEA; NEUTROPENIA; NON SMALL CELL LUNG CANCER; OVERALL SURVIVAL; PERIPHERAL EDEMA; PERIPHERAL NEUROPATHY; PHASE 2 CLINICAL TRIAL; PNEUMONIA; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PRURITUS; RANDOMIZED CONTROLLED TRIAL; RASH; SEPSIS; STEADY STATE; TREATMENT OUTCOME; UNSPECIFIED SIDE EFFECT; VOMITING; ANTAGONISTS AND INHIBITORS; CARCINOMA, NON-SMALL-CELL LUNG; CLINICAL TRIAL; COMPARATIVE STUDY; DISEASE COURSE; DISEASE FREE SURVIVAL; DRUG EFFECTS; ENZYMOLOGY; GENETICS; KAPLAN MEIER METHOD; LUNG NEOPLASMS; METABOLISM; MIDDLE AGED; MORTALITY; MUTATION; PATHOLOGY; SIGNAL TRANSDUCTION; TIME FACTOR;

ADULT; AGED; ANTINEOPLASTIC AGENTS, PHYTOGENIC; BIOMARKERS, TUMOR; CARCINOMA, NON-SMALL-CELL LUNG; DISEASE PROGRESSION; DISEASE-FREE SURVIVAL; FEMALE; HUMANS; KAPLAN-MEIER ESTIMATE; LUNG NEOPLASMS; MALE; MAP KINASE KINASE 1; MAP KINASE KINASE 2; MIDDLE AGED; MUTATION; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS P21(RAS); PYRIDONES; PYRIMIDINONES; SIGNAL TRANSDUCTION; TAXOIDS; TIME FACTORS; TREATMENT OUTCOME;

EID: 84929071676     PISSN: 09237534     EISSN: 15698041     Source Type: Journal    
DOI: 10.1093/annonc/mdv072     Document Type: Article

References (28)

1. Gainor JF, Varghese AM, Ou SH et al. ALK rearrangements are mutually exclusive with mutations in EGFR or KRAS: an analysis of 1,683 patients with non-small cell lung cancer. Clin Cancer Res 2013; 19: 4273-4281.
2. Riely GJ, Marks J, Pao W. KRAS mutations in non-small cell lung cancer. Proc Am Thorac Soc 2009; 6: 201-205.
3. Sanders HR, Albitar M. Somatic mutations of signaling genes in non-small-cell lung cancer. Cancer Genet Cytogenet 2010; 203: 7-15.
4. Okudela K, Woo T, Kitamura H. KRAS gene mutations in lung cancer: particulars established and issues unresolved. Pathol Int 2010; 60: 651-660.
5. Mascaux C, Iannino N, Martin B et al. The role of RAS oncogene in survival of patients with lung cancer: a systematic review of the literature with meta-analysis. Br J Cancer 2005; 92: 131-139.
6. Johnson ML, Sima CS, Chaft J et al. Association of KRAS and EGFR mutations with survival in patients with advanced lung adenocarcinomas. Cancer 2013; 119: 356-362.
7. Roberts PJ, Stinchcombe TE, Der CJ, Socinski MA. Personalized medicine in nonsmall-cell lung cancer: is KRAS a useful marker in selecting patients for epidermal growth factor receptor-targeted therapy? J Clin Oncol 2010; 28: 4769-4777.
8. Eberhard DA, Johnson BE, Amler LC et al. Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol 2005; 23: 5900-5909.
9. Massarelli E, Varella-Garcia M, Tang X et al. KRAS mutation is an important predictor of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. Clin Cancer Res 2007; 13: 2890-2896.
10. Jackman DM, Miller VA, Cioffredi LA et al. Impact of epidermal growth factor receptor and KRAS mutations on clinical outcomes in previously untreated nonsmall cell lung cancer patients: results of an online tumor registry of clinical trials. Clin Cancer Res 2009; 15: 5267-5273.
11. Paik PK, Johnson ML, D'Angelo SP et al. Driver mutations determine survival in smokers and never-smokers with stage IIIB/IV lung adenocarcinomas. Cancer 2012; 118: 5840-5847.
12. Ettinger DS, Akerley W, Borghaei H et al. Non-small cell lung cancer. J Natl Compr Canc Netw 2012; 10: 1236-1271.
13. Jing J, Greshock J, Holbrook JD et al. Comprehensive predictive biomarker analysis for MEK inhibitor GSK1120212. Mol Cancer Ther 2012; 11: 720-729.
14. Liu L, Gilmer T, Shi H et al. Preclinical modeling of susceptibility of NSCLC cells with RAS mutations to GSK1120212, a potent and selective MEK1/MEK2 inhibitor: implication for clinical development. In: 14th World Conference on Lung Cancer. Abstract MO04.11.
15. Liu L, Shi H, Zhang V, Gilmer T. Identification of molecular determinants of response to GSK1120212B, a potent and selective MEK inhibitor, as a single agent and in combination in RAS/RAF mutant nonsmall cell lung carcinoma cells. Cancer Res 2011; 71: 4394.
16. Infante JR, Fecher LA, Falchook GS et al. Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 dose-escalation trial. Lancet Oncol 2012; 13: 773-781.
17. Oken MM, Creech RH, Tormey DC et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982; 5: 649-655.
18. Eisenhauer EA, Therasse P, Bogaerts J et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45: 228-247.
19. Janne PA, Shaw AT, Pereira JR et al. Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebocontrolled, phase 2 study. Lancet Oncol 2013; 14: 38-47.
20. Flaherty KT, Robert C, Hersey P et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med 2012; 367: 107-114.
21. Carter CA, Rajan A, Szabo E et al. Two parallel randomized phase II studies of selumetinib (S) and erlotinib (E) in advanced non-small cell lung cancer selected by KRAS mutations. J Clin Oncol 2013; 31: 8026.
22. Garassino MC, Marabese M, Rusconi P et al. Different types of K-Ras mutations could affect drug sensitivity and tumour behaviour in non-small-cell lung cancer. Ann Oncol 2011; 22: 235-237.
23. Fiala O, Pesek M, Finek J et al. The dominant role of G12C over other KRAS mutation types in the negative prediction of efficacy of epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer. Cancer Genet 2013; 206: 26-31.
24. Ihle NT, Byers LA, Kim ES et al. Effect of KRAS oncogene substitutions on protein behavior: implications for signaling and clinical outcome. J Natl Cancer Inst 2012; 104: 228-239.
25. Holt SV, Logie 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 2012; 106: 858-866.
26. Gandara DR, Hiret S, Blumenschein GR et al. Oral MEK1/MEK2 inhibitor trametinib (GSK1120212) in combination with docetaxel in KRAS-mutant and wild-type (WT) advanced non-small cell lung cancer (NSCLC): a phase I/Ib trial. J Clin Oncol 2013; 31: 8028.
27. 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 2008; 14: 1351-1356.
28. Corcoran RB, Cheng KA, Hata AN et al. Synthetic lethal interaction of combined BCL-XL and MEK inhibition promotes tumor regressions in KRAS mutant cancer models. Cancer Cell 2013; 23: 121-128.