Factors predictive of response, disease progression, and overall survival after dabrafenib and trametinib combination treatment: a pooled analysis of individual patient data from randomised trials

The Lancet Oncology

Volumn 17, Issue 12, 2016, Pages 1743-1754

  Long, Georgina V ^a,b   Grob, Jean Jacques ^c   Nathan, Paul ^d   Ribas, Antoni ^e   Robert, Caroline ^f   Schadendorf, Dirk ^g,h   Lane, Stephen R ⁱ   Mak, Carmen ⁱ   Legenne, Philippe ⁱ   Flaherty, Keith T ^j   Davies, Michael A ^k  

^a UNIVERSITY OF SYDNEY   (Australia)

^b Royal North Shore and Mater Hospitals   (Australia)

^c TIMONE HOSPITAL   (France)

^d MOUNT VERNON CANCER CENTRE   (United Kingdom)

^e UNIVERSITY OF CALIFORNIA   (United States)

^f INSTITUT GUSTAVE ROUSSY   (France)

^g UNIVERSITY HOSPITAL ESSEN   (Germany)

^h GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

ⁱ NOVARTIS PHARMA AG   (Switzerland)

^j MASSACHUSETTS GENERAL HOSPITAL CANCER CENTER   (United States)

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

more..

Author keywords

[No Author keywords available]

Indexed keywords

COBIMETINIB; DABRAFENIB; IPILIMUMAB; LACTATE DEHYDROGENASE; MITOGEN ACTIVATED PROTEIN KINASE; TRAMETINIB; ANTINEOPLASTIC AGENT; B RAF KINASE; BRAF PROTEIN, HUMAN; IMIDAZOLE DERIVATIVE; OXIME; PYRIDONE DERIVATIVE; PYRIMIDINONE DERIVATIVE;

ADVANCED CANCER; ARTICLE; BRAIN METASTASIS; CANCER GRADING; CANCER PROGNOSIS; CONTROLLED STUDY; DISEASE COURSE; HUMAN; INTENTION TO TREAT ANALYSIS; MAJOR CLINICAL STUDY; MELANOMA; METASTASIS; MONOTHERAPY; OVERALL SURVIVAL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; RANDOMIZED CONTROLLED TRIAL; RETROSPECTIVE STUDY; RISK FACTOR; TREATMENT RESPONSE; FEMALE; GENETICS; MALE; MORTALITY; MUTATION; RANDOMIZED CONTROLLED TRIAL (TOPIC);

ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; DISEASE PROGRESSION; FEMALE; HUMANS; IMIDAZOLES; MALE; MELANOMA; MUTATION; OXIMES; PROTO-ONCOGENE PROTEINS B-RAF; PYRIDONES; PYRIMIDINONES; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RETROSPECTIVE STUDIES;

EID: 85003534271     PISSN: 14702045     EISSN: 14745488     Source Type: Journal    
DOI: 10.1016/S1470-2045(16)30578-2     Document Type: Article

References (34)

1. 1 Davies, H, Bignell, GR, Cox, C, et al. Mutations of the BRAF gene in human cancer. Nature 417 (2002), 949–954.
2. 2 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.
3. 3 Long, GV, Menzies, AM, Nagrial, AM, et al. Prognostic and clinicopathologic associations of oncogenic BRAF in metastatic melanoma. J Clin Oncol 29 (2011), 1239–1246.
4. 4 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.
5. 5 Long, GV, Weber, JS, Infante, JR, et al. Overall survival and durable responses in patients with BRAF V600-mutant metastatic melanoma receiving dabrafenib combined with trametinib. J Clin Oncol 34 (2016), 871–878.
6. 6 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.
7. 7 Long, GV, Stroyakovskiy, D, Gogas, H, et al. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med 371 (2014), 1877–1888.
8. 8 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.
9. 9 Robert, C, Karaszewska, B, Schachter, J, et al. Two year estimate of overall survival in COMBI-v, a randomized, open-label, phase III study comparing the combination of dabrafenib (D) and trametinib (T) with vemurafenib (vem) as first-line therapy in patients (pts) with unresectable or metastatic BRAF V600E/K mutation-positive cutaneous melanoma. Ann Oncol, 26, 2015, 3301 (abstr).
10. 10 Robert, C, Karaszewska, B, Schachter, J, et al. Three-year estimate of overall survival in COMBI-v, a randomized phase 3 study evaluating first-line dabrafenib (D) + trametinib (T) in patients (pts) with unresectable or metastatic BRAF V600E/K–mutant cutaneous melanoma. Ann Oncol, 27(suppl 6), 2016, LBA40 (abstr).
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 Robert, C, Long, GV, Brady, B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 372 (2015), 320–330.
13. 13 Robert, C, Schachter, J, Long, GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 372 (2015), 2521–2532.
14. 14 Larkin, J, Chiarion-Sileni, V, Gonzalez, R, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 373 (2015), 23–34.
15. 15 Larkin, J, Lao, CD, Urba, WJ, et al. Efficacy and safety of nivolumab in patients with BRAF V600 mutant and BRAF wild-type advanced melanoma: a pooled analysis of 4 clinical trials. JAMA Oncol 1 (2015), 433–440.
16. 16 Balch, CM, Gershenwald, JE, Soong, SJ, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 27 (2009), 6199–6206.
17. 17 Cox, DR, Oakes, D, Analysis of survival data, 1984, Chapman and Hall/CRC, Boca Raton, FL.
18. 18 Therneau, TM, Grambsch, PM, Modeling survival data: extending the Cox model, 2001, Springer, New York.
19. 19 Atkinson, EJ, Therneau, TM, An introduction to recursive partitioning using the RPART routines. Mayo Foundation. http://www.mayo.edu/research/documents/rpartminipdf/doc-10027257, 2000 (accessed Nov 1, 2016).
20. 20 Clark, LA, Pregibon, D, Tree-based models. Chambers, JM, Hastie, TJ, (eds.) Statistical models in S, 1992, Waswroth and Brooks, Pacific Grove, CA, 377–420.
21. 21 Daud, A, Weber, J, Sosman, J, et al. Updated overall survival for BRF113220: a phase 1–2 study of dabrafenib alone vs combined dabrafenib and trametinib in patients with BRAF V600 mutation-positive metastatic melanoma. Proc Am Soc Clin Oncol, 33(suppl), 2015, 9036 (abstr).
22. 22 Weide, B, Richter, S, Buttner, P, et al. Serum S100B, lactate dehydrogenase and brain metastasis are prognostic factors in patients with distant melanoma metastasis and systemic therapy. PLoS One, 8, 2013, e81624.
23. 23 Chan, MM, Haydu, LE, Menzies, AM, et al. The nature and management of metastatic melanoma after progression on BRAF inhibitors: effects of extended BRAF inhibition. Cancer 120 (2014), 3142–3153.
24. 24 Eigentler, TK, Figl, A, Krex, D, et al. Number of metastases, serum lactate dehydrogenase level, and type of treatment are prognostic factors in patients with brain metastases of malignant melanoma. Cancer 117 (2011), 1697–1703.
25. 25 Kelderman, S, Heemskerk, B, van Tinteren, H, et al. Lactate dehydrogenase as a selection criterion for ipilimumab treatment in metastatic melanoma. Cancer Immunol Immunother 63 (2014), 449–458.
26. 26 Joseph, RW, Elassaiss-Schaap, J, Wolchok, JD, et al. Baseline tumor size as an independent prognostic factor for overall survival in patients with metastatic melanoma treated with the anti-PD-1 monoclonal antibody MK-3475. Proc Am Soc Clin Oncol, 32(suppl 5), 2014, 3015 (abstr).
27. 27 Daud, A, Ribas, A, Robert, C, et al. Long-term efficacy of pembrolizumab (pembro; MK-3475) in a pooled analysis of 655 patients (pts) with advanced melanoma (MEL) enrolled in KEYNOTE-001. Proc Am Soc Clin Oncol, 33(suppl), 2015, 9005 (abstr).
28. 28 Larkin, J, Chiarion-Sileni, V, Gonzalez, R, et al. Efficacy and safety in key patient subgroups of nivolumab alone or combined with ipilimumab versus ipilimumab alone in treatment-naive patients with advanced melanoma (CheckMate 067). Ann Oncol 26:suppl 3 (2015), S664–S665 (abstr 3303).
29. 29 Weide, B, Martens, A, Hassel, JC, et al. Baseline biomarkers for outcome of melanoma patients treated with pembrolizumab. Clin Cancer Res, 2016, 10.1158/1078-0432.CCR-16-0127 published online May 16.
30. 30 Weber, JS, D'Angelo, SP, Minor, D, et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol 16 (2015), 375–384.
31. 31 Johnson, DB, Lovly, CM, Flavin, M, et al. Impact of NRAS mutations for patients with advanced melanoma treated with immune therapies. Cancer Immunol Res 3 (2015), 288–295.
32. 32 Joseph, RW, Sullivan, RJ, Harrell, R, Correlation of NRAS mutations with clinical response to high-dose IL-2 in patients with advanced melanoma. J Immunother 35 (2012), 66–72.
33. 33 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.
34. 34 Grob, JJ, Long, GV, Schadendorf, D, Flaherty, K, Disease kinetics for decision-making in advanced melanoma: a call for scenario-driven strategy trials. Lancet Oncol 16 (2015), e522–e526.