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
N (%) | HR | 95% CI | p value | |
---|---|---|---|---|
LDH at baseline* | ||||
<1 ULN | 115 (41.8) | 1 (=reference) | - | - |
[1 - 2[ ULN | 50 (18.2) | 1.30 | [0.83 - 2.04] | 0.2473 |
≥2 ULN | 21 (7.6) | 2.50 | [1.37 - 4.58] | 0.0030 |
Missing | 89 (32.4) | 1.44 | [0.99 - 2.10] | 0.0571 |
ECOG PS* | ||||
O | 144 (52.4) | 1 (=reference) | - | - |
1 | 91 (33.1) | 1.36 | [0.94 - 1.96] | 0.0995 |
≥2 | 40 (14.6) | 2.17 | [1.37 - 3.44] | 0.0010 |
Metastatic sites* | ||||
<3 | 84 (30.6) | 1 (=reference) | - | - |
≥3 | 191 (69.5) | 1.58 | [1.10 - 2.28] | 0.0142 |
Status | ||||
Naïve | 121 (44.0) | 1 (=reference) | - | - |
Non naïve | 154 (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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