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Poster Display session 3

1885 - Factors associated with disease progression in patients treated with trametinib in combination with dabrafenib for unresectable advanced BRAFV600-mutant melanoma: an open label, non randomized study


30 Sep 2019


Poster Display session 3


Tumour Site



Philippe Saiag


Annals of Oncology (2019) 30 (suppl_5): v533-v563. 10.1093/annonc/mdz255


P. Saiag1, C. Robert2, J.J. Grob3, L. Mortier4, O. Dereure5, C. Lebbe6, S. Mansard7, F. Grange8, E. Neidhardt9, T. Lesimple10, L. Machet11, C. Bedane12, H. Maillard13, S. Dalac-Rat14, C. Nardin15, A. Szenik16, A. Denden17, C. Dutriaux18

Author affiliations

  • 1 Department Of Dermatology, Hopital Ambroise Pare, 92100 - Boulogne-Billancourt/FR
  • 2 Dermatology Department, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 3 Dermatology And Skin Cancer, Hôpital de la Timone, 13009 - Marseille/FR
  • 4 Department Of Dermatology, Hopital Claude Huriez, 59037 - Lille/FR
  • 5 Dermatology And Skin Cancer, Hopital Saint-Eloi (Montpellier), 34295 - Montpellier/FR
  • 6 Department Of Dermatology, Hôpital Saint Louis, 75010 - Paris/FR
  • 7 Department Of Dermatology, CHU Estaing, 63003 - Clermont-Ferrand/FR
  • 8 Dermatology, CHU Reims–Hôpital Robert Debre, 51100 - Reims/FR
  • 9 Department Of Dermatology, Centre Léon Bérard, 69008 - Lyon/FR
  • 10 Department Of Medical Oncology, Centre Eugene - Marquis, 35042 - Rennes/FR
  • 11 Department Of Dermatology, CHRU Tours, 37044 - Tours Cedex/FR
  • 12 Department Of Dermatology, CHU Limoges - Hopital Dupuytren, 87042 - Limoges/FR
  • 13 Department Of Dermatology, CHU Le Mans, 72100 - Le Mans/FR
  • 14 Department Of Dermatology, CHU Dijon, 21000 - Dijon/FR
  • 15 Dermatology, CHU de Besançon, 25030 - Besançon/FR
  • 16 Oncology Department, Novartis Pharma - France, 92500 - Rueil-Malmaison/FR
  • 17 Oncology Department, Novartis Pharma S.A.S., 92500 - Rueil-Malmaison/FR
  • 18 Department Of Dermatology, CHU Bordeaux - Hopital St. André, 33000 - Bordeaux/FR


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Abstract 1885


BRAF and MEK inhibitors dabrafenib (D) and trametinib (T) have transformed BRAFV600-mutant melanoma patients’ (pts) treatment. In a large prospective trial of pts treated with combination D+T, which also included pts with brain metastasis (BM), we assessed factors associated with progression and stratified the population into risk groups using regression tree analysis (RTA).


This phase IIIb single arm, open label, multicenter, French study included in 40 centers pts with histologically confirmed unresectable stage IIIc or IV BRAFV600-mutant melanoma. Selection criteria allowed presence of BM, ECOG ≤2, previous advanced melanoma treatments (except BRAFi+MEKi combination). Progression-free survival (PFS) was estimated using the Kaplan Meier analysis and modeled with multivariate Cox regression model. Risk subgroups were identified using an exponential RTA. Significance was set at p < 0.05.


Between March 2015 and November 2016, 914 pts were screened and 856 received at least 1 dose of D+T. Overall, 92% of pts had AJCC stage IV melanoma, 38% ECOG ≥1 and 32% BM. Among the 587 pts with known LDH at baseline, 38% had >ULN. Median PFS was 8.02 months (95%CI, 7.33-8.77). Significant independent factors associated with lower PFS were ECOG ≥1, elevated serum LDH, ≥3 metastatic sites, and presence of BM (Table). Pts with <3 metastatic sites, ECOG 0 and absence of BM had the highest probability of PFS at 6 (83% [95% CI, 76-87]) and 12 months (56% [95% CI, 47-64]). No unexpected AE were reported.Table:

1338P Multivariate Cox proportional hazards analysis of PFS by prognostic factors - All Subjects Treated Population (N = 856)

N (%)HR95% CIp value
LDH at baseline*
<1 ULN366 (42.8)1 (=reference)--
[1 - 2[ ULN160 (18.7)1.64[1.26 - 2.14]0.0003
≥2 ULN61 (7.1)2.45[1.70 - 3.53]<.0001
Missing269 (31.4)1.34[1.05 - 1.71]0.0167
0531 (62.0)1 (=reference)--
1242 (28.3)1.49[1.19 - 1.87]0.0005
≥283 (9.7)2.32[1.69 - 3.19]<.0001
Metastatic sites*
<3344 (40.2)1 (=reference)--
≥3445 (52.0)1.61[1.28 - 2.02]<.0001
Missing67 (7.8)1.05[0.63 - 1.74]0.8494
Presence of brain metastasis*
No579 (67.6)1 (=reference)--
Yes275 (32.1)1.38[1.11 - 1.71]0.0043
Missing2 (0.23)---

Factors included in the RTA.


This is to date the largest prospective study in advanced BRAFV600-mutant melanoma pts treated with D+T. The study was carried out in conditions close to the real-world. We confirm findings of registration trials that LDH, ECOG and ≥3 metastatic sites are associated with shorter PFS, but the real-world setting introduces BM as a major prognostic factor.

Clinical trial identification

Editorial acknowledgement

Jone Iriondo-Alberdi (PhD) from ITEC Services.

Legal entity responsible for the study

Novartis Pharma S.A.S. (France).


Novartis Pharma S.A.S. (France).


P. Saiag: Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses, Non-remunerated activity/ies: Bristol-Myers Squibb; Travel / Accommodation / Expenses, Non-remunerated activity/ies: Merck Sharp & Dohme ; Travel / Accommodation / Expenses: Merck Serono; Travel / Accommodation / Expenses: Pfizer; Research grant / Funding (self), Travel / Accommodation / Expenses, Non-remunerated activity/ies: Roche-Genentech; Travel / Accommodation / Expenses: Pierre Fabre; Travel / Accommodation / Expenses, Non-remunerated activity/ies: Novartis. C. Robert: Advisory / Consultancy: Roche; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Merck Sharp & Dohme ; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Novartis; Advisory / Consultancy: Amgen; Advisory / Consultancy, Participation to Boards and Steering Committees: Pierre Fabre. J.J. Grob: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Sharp & Dohme ; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Incyte. L. Mortier: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: GSK/Novartis; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Leo; Honoraria (self): Merck Serono; Honoraria (self): Sanofi; Honoraria (self): Pierre Fabre; Honoraria (self): Novartis. C. Lebbe: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Travel / Accommodation / Expenses: Merck Sharp & Dohme ; Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): Amgen; Honoraria (self): Merck; Honoraria (self): Pierre Fabre; Honoraria (self): Pfizer; Honoraria (self): Incyte. S. Mansard: Advisory / Consultancy: Novartis. F. Grange: Advisory / Consultancy: Novartis. E. Neidhardt: Travel / Accommodation / Expenses: BMS. T. Lesimple: Advisory / Consultancy: Novartis; Advisory / Consultancy: MSD; Advisory / Consultancy: Incyte; Advisory / Consultancy: Pierre Fabre; Research grant / Funding (self): Roche. C. Bedane: Advisory / Consultancy: Novartis. S. Dalac-Rat: Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche; Advisory / Consultancy: BMS; Advisory / Consultancy: Pierre Fabre. C. Nardin: Advisory / Consultancy: Novartis; Advisory / Consultancy: BMS; Advisory / Consultancy: MSD. A. Szenik: Full / Part-time employment: Novartis. A. Denden: Full / Part-time employment: Novartis. C. Dutriaux: Honoraria (self), Advisory / Consultancy: Novartis. All other authors have declared no conflicts of interest.

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