Dabrafenib plus trametinib in patients with previously treated BRAFV600E-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial

The Lancet Oncology

Volumn 17, Issue 7, 2016, Pages 984-993

  Planchard, David ^a   Besse, Benjamin ^a,b   Groen, Harry J M ^c,d   Souquet, Pierre Jean ^e   Quoix, Elisabeth ^f   Baik, Christina S ^g   Barlesi, Fabrice ^h   Kim, Tae Min ⁱ   Mazieres, Julien ^j,k   Novello, Silvia ^l   Rigas, James R ^m   Upalawanna, Allison ⁿ   D'Amelio, Anthony M ⁿ   Zhang, Pingkuan ⁿ   Mookerjee, Bijoyesh ⁿ   Johnson, Bruce E ^o  

^a INSTITUT GUSTAVE ROUSSY   (France)

^b UNIVERSITÉ PARIS SACLAY   (France)

^c UNIVERSITY OF GRONINGEN   (Netherlands)

^d UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

^e CENTRE HOSPITALIER LYON SUD   (France)

^f HÔPITAL CIVIL   (France)

^g UNIVERSITY OF WASHINGTON   (United States)

^h AIX MARSEILLE UNIVERSITY   (France)

ⁱ Seoul National University Hospital   (South Korea)

^j SERVICE DE PNEUMOLOGIE   (France)

^k UNIVERSITÉ PAUL SABATIER   (France)

^l UNIVERSITY OF TURIN   (Italy)

^m DARTMOUTH MEDICAL SCHOOL   (United States)

ⁿ NOVARTIS PHARMA AG   (Switzerland)

^o DANA FARBER CANCER INSTITUTE   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE AMINOTRANSFERASE; ALKALINE PHOSPHATASE; AMYLASE; ASPARTATE AMINOTRANSFERASE; B RAF KINASE; C REACTIVE PROTEIN; DABRAFENIB; GAMMA GLUTAMYLTRANSFERASE; TRAMETINIB; ANTINEOPLASTIC AGENT; BRAF PROTEIN, HUMAN; IMIDAZOLE DERIVATIVE; OXIME; PYRIDONE DERIVATIVE; PYRIMIDINONE DERIVATIVE; TUMOR MARKER;

ACUTE CHOLECYSTITIS; ADULT; AGED; ALKALINE PHOSPHATASE BLOOD LEVEL; AMYLASE BLOOD LEVEL; ANEMIA; ARTHRALGIA; ARTICLE; ASTHENIA; BACKACHE; BASAL CELL CARCINOMA; BRAF GENE; BRAIN METASTASIS; CHILL; CONFUSION; CONSTIPATION; CORONARY ARTERY OBSTRUCTION; COUGHING; CREATININE BLOOD LEVEL; DEATH; DECREASED APPETITE; DEHYDRATION; DIARRHEA; DIZZINESS; DRUG EFFICACY; DRUG RESPONSE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DRY SKIN; DYSGEUSIA; DYSPNEA; ERYTHEMA NODOSUM; FATIGUE; FEBRILE NEUTROPENIA; FEMALE; FEVER; GENE MUTATION; HEADACHE; HEART VENTRICLE FIBRILLATION; HEMATURIA; HEMOPTYSIS; HIP FRACTURE; HUMAN; HYPERCALCEMIA; HYPERKERATOSIS; HYPERTENSION; HYPERTRANSAMINASEMIA; HYPONATREMIA; HYPOPHOSPHATEMIA; HYPOTENSION; INCISIONAL HERNIA; INTERSTITIAL NEPHRITIS; INTESTINE OBSTRUCTION; KIDNEY FAILURE; LEGIONNAIRE DISEASE; LEUKOPENIA; LIVER CELL CARCINOMA; LUNG EMBOLISM; LUNG METASTASIS; MAJOR CLINICAL STUDY; MALE; MOLECULARLY TARGETED THERAPY; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; MUSCLE SPASM; MYALGIA; NAUSEA; NEUTROPENIA; NON SMALL CELL LUNG CANCER; OPEN STUDY; OVERALL SURVIVAL; PAIN; PANCYTOPENIA; PERIPHERAL EDEMA; PERIPHERAL NEUROPATHY; PHASE 2 CLINICAL TRIAL; PLEURA EFFUSION; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PRURITUS; PYELONEPHRITIS; QUADRIPLEGIA; RASH; RESPIRATORY DISTRESS; RETROPERITONEAL HEMORRHAGE; SIDE EFFECT; SKIN CARCINOMA; SUBARACHNOID HEMORRHAGE; THORAX PAIN; THROMBOCYTOPENIA; TUMOR GROWTH; UPPER ABDOMINAL PAIN; VERTIGO; VISUAL IMPAIRMENT; VOMITING; WEIGHT GAIN; WEIGHT REDUCTION; ADENOCARCINOMA; CANCER STAGING; CARCINOMA, LARGE CELL; CARCINOMA, NON-SMALL-CELL LUNG; CLINICAL TRIAL; FOLLOW UP; GENETICS; LUNG NEOPLASMS; LYMPH NODE METASTASIS; MIDDLE AGED; MUTATION; PATHOLOGY; PROGNOSIS; SECONDARY; SURVIVAL RATE; TUMOR RECURRENCE;

ADENOCARCINOMA; ADULT; AGED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BIOMARKERS, TUMOR; CARCINOMA, LARGE CELL; CARCINOMA, NON-SMALL-CELL LUNG; FEMALE; FOLLOW-UP STUDIES; HUMANS; IMIDAZOLES; LUNG NEOPLASMS; LYMPHATIC METASTASIS; MALE; MIDDLE AGED; MUTATION; NEOPLASM RECURRENCE, LOCAL; NEOPLASM STAGING; OXIMES; PROGNOSIS; PROTO-ONCOGENE PROTEINS B-RAF; PYRIDONES; PYRIMIDINONES; SURVIVAL RATE;

EID: 84991059363     PISSN: 14702045     EISSN: 14745488     Source Type: Journal    
DOI: 10.1016/S1470-2045(16)30146-2     Document Type: Article

References (37)

1. 1 Siegel, RL, Miller, KD, Jemal, A, Cancer statistics, 2016. CA Cancer J Clin 66 (2016), 7–30.
2. 2 Rosell, R, Carcereny, E, Gervais, R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 13 (2012), 239–246.
3. 3 Shaw, AT, Kim, DW, Nakagawa, K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med 368 (2013), 2385–2394.
4. 4 Davies, H, Bignell, GR, Cox, C, et al. Mutations of the BRAF gene in human cancer. Nature 417 (2002), 949–954.
5. 5 Barlesi, F, Mazieres, J, Merlio, JP, et al. Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT). Lancet 387 (2016), 1415–1426.
6. 6 Kris, MG, Johnson, BE, Berry, LD, et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA 311 (2014), 1998–2006.
7. 7 Paik, PK, Arcila, ME, Fara, M, et al. Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. J Clin Oncol 29 (2011), 2046–2051.
8. 8 Cardarella, S, Ogino, A, Nishino, M, et al. Clinical, pathologic, and biologic features associated with BRAF mutations in non-small cell lung cancer. Clin Cancer Res 19 (2013), 4532–4540.
9. 9 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 (2011), 3574–3579.
10. 10 Flaherty, KT, Infante, JR, Daud, A, et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med 367 (2012), 1694–1703.
11. 11 Larkin, J, Ascierto, PA, Dréno, B, et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med 371 (2014), 1867–1876.
12. 12 Long, GV, Stroyakovskiy, D, Gogas, H, et al. Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial. Lancet 386 (2015), 444–451.
13. 13 Planchard, D, Min Kim, T, Mazieres, J, Quiox, E, Riely, G, Barlesi, F, Dabrafenib in BRAF V600E–mutant advanced non-small cell lung cancer: an open-label, single arm, multicenter, phase 2 trial. Lancet Oncol 17 (2016), 642–650.
14. 14 Green, SJ, Dahlberg, S, Planned versus attained design in phase II clinical trials. Stat Med 11 (1992), 853–862.
15. 15 Brookmeyer, R, Crowley, J, A confidence interval for the mean survival time. Biometrics 38 (1982), 29–41.
16. 16 Yao, Z, Torres, NM, Tao, A, et al. BRAF mutants evade ERK-dependent feedback by different mechanisms that determine their sensitivity to pharmacologic inhibition. Cancer Cell 28 (2015), 370–383.
17. 17 Hyman, DM, Puzanov, I, Subbiah, V, et al. Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N Engl J Med 373 (2015), 726–736.
18. 18 Gautschi, O, Milia, J, Cabarrou, B, et al. Targeted therapy for patients with BRAF-mutant lung cancer: results from the European EURAF cohort. J Thorac Oncol 10 (2015), 1451–1457.
19. 19 Sullivan, RJ, Flaherty, KT, Resistance to BRAF-targeted therapy in melanoma. Eur J Cancer 49 (2013), 1297–1304.
20. 20 Wu, YL, Zhou, C, Hu, CP, et al. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol 15 (2014), 213–222.
21. 21 Maemondo, M, Inoue, A, Kobayashi, K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 362 (2010), 2380–2388.
22. 22 Shaw, AT, Ou, SH, Bang, YJ, et al. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med 371 (2014), 1963–1971.
23. 23 Awad, MM, Oxnard, GR, Jackman, DM, et al. MET exon 14 mutations in non-small-cell lung cancer are associated with advanced age and stage-dependent MET genomic amplification and c-Met overexpression. J Clin Oncol 34 (2016), 721–730.
24. 24 Jorge, SE, Schulman, S, Freed, JA, et al. Responses to the multitargeted MET/ALK/ROS1 inhibitor crizotinib and co-occurring mutations in lung adenocarcinomas with MET amplification or MET exon 14 skipping mutation. Lung Cancer 90 (2015), 369–374.
25. 25 Paik, PK, Drilon, A, Fan, PD, et al. Response to MET inhibitors in patients with stage IV lung adenocarcinomas harboring MET mutations causing exon 14 skipping. Cancer Discov 5 (2015), 842–849.
26. 26 Nguyen-Ngoc, T, Bouchaab, H, Adjei, AA, Peters, S, BRAF alterations as therapeutic targets in non-amall-cell lung cancer. J Thorac Oncol 10 (2015), 1396–1403.
27. 27 Jakob, JA, Bassett, RL Jr, Ng, CS, et al. NRAS mutation status is an independent prognostic factor in metastatic melanoma. Cancer 118 (2012), 4014–4023.
28. 28 Oxnard, GR, Paweletz, CP, Kuang, Y, et al. Noninvasive detection of response and resistance in EGFR-mutant lung cancer using quantitative next-generation genotyping of cell-free plasma DNA. Clin Cancer Res 20 (2014), 1698–1705.
29. 29 Solomon, BJ, Mok, T, Kim, DW, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med 371 (2014), 2167–2177.
30. 30 Herbst, RS, Baas, P, Kim, DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 387 (2015), 1540–1550.
31. 31 Garon, EB, Rizvi, NA, Hui, R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 372 (2015), 2018–2028.
32. 32 Borghaei, H, Paz-Ares, L, Horn, L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 373 (2015), 1627–1639.
33. 33 Robert, C, Karaszewska, B, Schachter, J, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med 372 (2015), 30–39.
34. 34 Menzies, AM, Ashworth, MT, Swann, S, et al. Characteristics of pyrexia in BRAFV600E/K metastatic melanoma patients treated with combined dabrafenib and trametinib in a phase I/II clinical trial. Ann Oncol 26 (2015), 415–421.
35. 35 Lito, P, Pratilas, CA, Joseph, EW, et al. Relief of profound feedback inhibition of mitogenic signaling by RAF inhibitors attenuates their activity in BRAFV600E melanomas. Cancer Cell 22 (2012), 668–682.
36. 36 Garon, EB, Ciuleanu, TE, Arrieta, O, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet 384 (2014), 665–673.
37. 37 Mekinist (trametinib) package insert. Novartis Pharmaceuticals Corporation East Hanover, New Jersey 07936. https://www.pharma.us.novartis.com/product/pi/pdf/mekinist.pdf, 2015 (accessed April 28, 2016).