Clinical, molecular, and immune analysis of dabrafenib-Trametinib combination treatment for braf inhibitor-refractorymetastatic melanoma a phase 2 clinical trial

JAMA Oncology

Volumn 2, Issue 8, 2016, Pages 1056-1064

  Chen, Guo ^a   McQuade, Jennifer L ^a   Panka, David J ^b   Hudgens, Courtney W ^a   Amin Mansour, Ali ^c   Jasmine Mu, Xinmeng ^a   Bahl, Samira ^a   Jané Valbuena, Judit ^a   Wani, Khalida M ^a   Reuben, Alexandre ^c   Creasy, Caitlyn A ^a   Jiang, Hong ^a   Cooper, Zachary A ^a   Roszik, Jason ^a   Bassett, Roland L ^a   Joon, Aron Y ^b   Simpson, Lauren M ^a   Mouton, Rosalind D ^a   Glitza, Isabella C ^a   Patel, Sapna P ^a   Hwu, Wen Jen ^a   Amaria, Rodabe N ^a   Diab, Adi ^a   Hwu, Patrick ^a   Lazar, Alexander J ^a   Wargo, Jennifer A ^a   Garraway, Levi A ^a   Tetzlaff, Michael T ^a   Sullivan, Ryan J ^d   Kim, Kevin B ^e   Davies, Michael A ^a   more..

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

^c BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^d MASSACHUSETTS GENERAL HOSPITAL   (United States)

^e CALIFORNIA PACIFIC MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AKT1S1 PROTEIN, HUMAN; ANTINEOPLASTIC AGENT; B RAF KINASE; BRAF PROTEIN, HUMAN; CD274 PROTEIN, HUMAN; CD8 ANTIGEN; DABRAFENIB; IMIDAZOLE DERIVATIVE; MAPK1 PROTEIN, HUMAN; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; OXIME; PROGRAMMED DEATH 1 LIGAND 1; PROTEIN KINASE INHIBITOR; PROTEIN S6; PYRIDONE DERIVATIVE; PYRIMIDINONE DERIVATIVE; SIGNAL TRANSDUCING ADAPTOR PROTEIN; TRAMETINIB;

ADULT; ANTAGONISTS AND INHIBITORS; CLINICAL TRIAL; DISEASE FREE SURVIVAL; DRUG RESISTANCE; FEMALE; GENETICS; HUMAN; IMMUNOHISTOCHEMISTRY; IMMUNOLOGY; MALE; MELANOMA; METABOLISM; MIDDLE AGED; PATHOLOGY; PHASE 2 CLINICAL TRIAL; PHOSPHORYLATION; PROSPECTIVE STUDY; SECONDARY; SIGNAL TRANSDUCTION; SKIN NEOPLASMS; TREATMENT OUTCOME;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ADULT; ANTIGENS, CD274; ANTIGENS, CD8; ANTINEOPLASTIC AGENTS; DISEASE-FREE SURVIVAL; DRUG RESISTANCE, NEOPLASM; FEMALE; HUMANS; IMIDAZOLES; IMMUNOHISTOCHEMISTRY; MALE; MAP KINASE SIGNALING SYSTEM; MELANOMA; MIDDLE AGED; MITOGEN-ACTIVATED PROTEIN KINASE 1; MITOGEN-ACTIVATED PROTEIN KINASE 3; MITOGEN-ACTIVATED PROTEIN KINASES; OXIMES; PHOSPHORYLATION; PROSPECTIVE STUDIES; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS B-RAF; PYRIDONES; PYRIMIDINONES; RIBOSOMAL PROTEIN S6; SIGNAL TRANSDUCTION; SKIN NEOPLASMS; TREATMENT OUTCOME;

EID: 85011960917     PISSN: 23742437     EISSN: 23742445     Source Type: Journal    
DOI: 10.1001/jamaoncol.2016.0509     Document Type: Article

References (33)

1. Cancer Genome Atlas Network. Genomic classification of cutaneous melanoma. Cell. 2015;161 (7):1681-1696.
2. Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417 (6892):949-954.
3. Robert C, Karaszewska B, Schachter J, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015;372(1):30-39.
4. Larkin J, Ascierto PA, Dréno B, et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med. 2014;371(20):1867-1876.
5. Poulikakos PI, Persaud Y, Janakiraman M, et al. RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E). Nature. 2011;480(7377):387-390.
6. Shi H, Moriceau G, Kong X, et al. Melanoma whole-exome sequencing identifies (V600E)B-RAF amplification-mediated acquired B-RAF inhibitor resistance. Nat Commun. 2012;3:724.
7. Shi H, HugoW, Kong X, et al. Acquired resistance and clonal evolution in melanoma during BRAF inhibitor therapy. Cancer Discov. 2014;4(1):80-93.
8. Nazarian R, Shi H, Wang Q, et al. Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. Nature. 2010;468 (7326):973-977.
9. Emery CM, Vijayendran KG, Zipser MC, et al. MEK1 mutations confer resistance to MEK and B-RAF inhibition. Proc Natl Acad Sci U S A. 2009; 106(48):20411-20416.
10. CarlinoMS, Fung C, Shahheydari H, et al. Preexisting MEK1P124 mutations diminish response to BRAF inhibitors in metastatic melanoma patients. Clin Cancer Res. 2015;21(1):98-105.
11. Wagle N, Emery C, Berger MF, et al. Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling. J Clin Oncol. 2011;29(22):3085-3096.
12. Johannessen CM, Boehm JS, Kim SY, et al. COT drives resistance to RAF inhibition through MAP kinase pathway reactivation. Nature. 2010;468 (7326):968-972.
13. Villanueva J, Vultur A, Lee JT, et al. Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma can be overcome by cotargeting MEK and IGF-1R/PI3K. Cancer Cell. 2010;18(6):683-695.
14. Paraiso KH, Fedorenko IV, Cantini LP, et al. Recovery of phospho-ERK activity allows melanoma cells to escape from BRAF inhibitor therapy. Br J Cancer. 2010;102(12):1724-1730.
15. Kwong LN, Boland GM, Frederick DT, et al. Co-clinical assessment identifies patterns of BRAF inhibitor resistance in melanoma. J Clin Invest. 2015;125(4):1459-1470.
16. Knight DA, Ngiow SF, LiM, et al. Host immunity contributes to the anti-melanoma activity of BRAF inhibitors. J Clin Invest. 2013;123(3):1371-1381.
17. Long GV, Stroyakovskiy D, Gogas H, et al. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med. 2014; 371(20):1877-1888.
18. Johnson DB, Flaherty KT, Weber JS, et al. Combined BRAF (dabrafenib) and MEK inhibition (trametinib) in patients with BRAFV600-mutant melanoma experiencing progression with single-Agent BRAF inhibitor. J Clin Oncol. 2014;32 (33):3697-3704.
19. 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(2):228-247.
20. Trotti A, Colevas AD, Setser A, et al. CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol. 2003;13(3):176-181.
21. Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61-70.
22. Panka DJ, Buchbinder E, Giobbie-Hurder A, et al. Clinical utility of a blood-based BRAF(V600E) mutation assay in melanoma. Mol Cancer Ther. 2014;13(12):3210-3218.
23. Pratilas CA, Taylor BS, Ye Q, et al. (V600E)BRAF is associated with disabled feedback inhibition of RAF-MEK signaling and elevated transcriptional output of the pathway. Proc Natl Acad Sci U S A. 2009;106(11):4519-4524.
24. Chen K, Meric-Bernstam F, Zhao H, et al. Clinical actionability enhanced through deep targeted sequencing of solid tumors. Clin Chem. 2015;61(3):544-553.
25. The R Foundation R: A language and environment for statistical computing. 2015; https: //www.R-project.org/. Accessed June 4, 2015.
26. Bollag G, Hirth P, Tsai J, et al. Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature. 2010;467(7315): 596-599.
27. Trunzer K, Pavlick AC, Schuchter L, et al. Pharmacodynamic effects and mechanisms of resistance to vemurafenib in patients with metastatic melanoma. J Clin Oncol. 2013;31(14): 1767-1774.
28. Morris EJ, Jha S, Restaino CR, et al. Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors. Cancer Discov. 2013;3(7):742-750.
29. Johnson DB, Menzies AM, Zimmer L, et al. BRAF inhibitor acquired resistance: A multicenter meta-Analysis of the spectrum and clinical implications of resistance mechanisms. J Clin Oncol. 2015;33(suppl):abstract 9008.
30. CarlinoMS, Todd JR, Gowrishankar K, et al. Differential activity of MEK and ERK inhibitors in BRAF inhibitor resistant melanoma. Mol Oncol. 2014;8(3):544-554.
31. Wagle N, Van Allen EM, Treacy DJ, et al. MAP kinase pathway alterations in BRAF-mutant melanoma patients with acquired resistance to combined RAF/MEK inhibition. Cancer Discov. 2014;4(1):61-68.
32. Watson IR, Li L, Cabeceiras PK, et al. The RAC1 P29S hotspot mutation in melanoma confers resistance to pharmacological inhibition of RAF. Cancer Res. 2014;74(17):4845-4852.
33. Frederick DT, Piris A, Cogdill AP, et al. BRAF inhibition is associated with enhanced melanoma antigen expression and a more favorable tumor microenvironment in patients with metastatic melanoma. Clin Cancer Res. 2013;19(5):1225-1231.