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Poster Display session 3

3036 - An open-label, non-randomized, phase IIIb study of trametinib in combination with dabrafenib for patients with unresectable advanced BRAFV600-mutant melanoma: a subgroup analysis of patients with brain metastasis

Date

30 Sep 2019

Session

Poster Display session 3

Presenters

Caroline Dutriaux

Citation

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

Authors

C. Dutriaux1, 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, P. Saiag18

Author affiliations

  • 1 Department Of Dermatology, CHU Bordeaux - Hopital St. André, 33000 - Bordeaux/FR
  • 2 Dermatology Department, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 3 Dermatology And Skin Cancer, Hopital St. Marguerite Assistance Publique Hopitaux de Marseille, 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, Novartis Pharma S.A.S., 92500 - Rueil-Malmaison/FR
  • 18 Department Of Dermatology, Hopital Ambroise Pare, 92100 - Boulogne-Billancourt/FR
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Abstract 3036

Background

Thirty to 60% of stage unresectable AJCC III and IV melanoma patients (pts) develop brain metastases (BM). This population has been excluded from most clinical trials. Using a large prospective trial including pts with advanced BRAFV600-mutant melanoma and allowing for BM, we assessed in the BM population factors associated with disease progression and stratified the population into risk groups using regression tree analysis (RTA).

Methods

This phase IIIb single arm, open label, multicenter, non randomized French study included pts with unresectable stage IIIc or IV BRAFV600-mutant melanoma. Selection criteria allowed for BM, ECOG ≤2, previous advanced melanoma treatments. Pts received dabrafenib (D) + trametinib (T) until progression. Progression-free survival (PFS) was estimated using the Kaplan Meier analysis and modeled with a multivariate Cox regression model. Risk subgroups were identified using an exponential RTA. Significance was set at p < 0.05.

Results

Between March 2015 and November 2016, 856 pts were included and 275 (32%) had BM. Median PFS was 5.68 months (95% CI, 5.29-6.87) in the BM population. Significant independent factors associated with lower PFS were ECOG ≥1, elevated serum LDH, ≥3 metastatic sites, and non naïve status (Table). Pts with ECOG 0, <3 metastatic sites, LDH Multivariate Cox proportional hazards analysis of PFS by prognostic factors

N (%)HR95% CIp value
LDH at baseline*
<1 ULN115 (41.8)1 (=reference)--
[1 - 2[ ULN50 (18.2)1.30[0.83 - 2.04]0.2473
≥2 ULN21 (7.6)2.50[1.37 - 4.58]0.0030
Missing89 (32.4)1.44[0.99 - 2.10]0.0571
ECOG PS*
O144 (52.4)1 (=reference)--
191 (33.1)1.36[0.94 - 1.96]0.0995
≥240 (14.6)2.17[1.37 - 3.44]0.0010
Metastatic sites*
<384 (30.6)1 (=reference)--
≥3191 (69.5)1.58[1.10 - 2.28]0.0142
Status
Naïve121 (44.0)1 (=reference)--
Non naïve154 (56.0)1.60[1.14 - 2.25]0.0061
*

Factors included in the RTA.

Conclusions

To our knowledge, this is the first analysis from the largest prospective study in BRAF-mutated melanoma pts with BM. The study was carried out in difficult-to-treat pts and in conditions that were close to the real-world setting. ECOG >1, ≥3 metastatic sites and elevated LDH were associated with shorter PFS, a finding previously demonstrated only in pts without BM. Regression trees will be presented.

Clinical trial identification

Editorial acknowledgement

Jone Iriondo-Alberdi (PhD) from ITEC Services.

Legal entity responsible for the study

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

Funding

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

Disclosure

C. Dutriaux: Honoraria (self), Advisory / Consultancy: 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: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: GSK/Novartis; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Leo; Honoraria (self): Sanofi; Honoraria (self): Novartis; Honoraria (self): Pierre Fabre; Honoraria (self): Merck Serono. 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: Honoraria (self): 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: Bristol-Myers Squibb; Advisory / Consultancy: Merck Sharp & Dohme . A. Szenik: Full / Part-time employment: Novartis. A. Denden: Full / Part-time employment: Novartis. 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: Novartis. All other authors have declared no conflicts of interest.

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