Abstract 1122P
Background
Despite the availability of improved treatment options in BRAFV600 mutation-positive metastatic melanoma, limited evidence exists for the treatment of melanoma patients (pts) with brain metastases (BMs). The non-interventional study COMBI-r evaluates the treatment of BRAFV600-mutated melanoma with the BRAF/MEK inhibitor combination dabrafenib plus trametinib (D+T) in clinical routine. A recent analysis confirmed the effectiveness and safety of D+T. Here, we focus on real-world demographics and outcomes of melanoma pts with and without (w/o) BMs.
Methods
Between Dec 2015 and Dec 2018, 502 pts at 58 German centers were included in COMBI-r. Effectiveness and safety of D+T were assessed in pts treated for at least 1 year or who had stopped treatment. 273 pts had stage IV disease at baseline; 100 pts had BMs and 173 pts had no BMs. Effectiveness of D+T and demographics were described and integrated with slow, intermediate and fast tumor dynamics, which were based on the physician’s objective assessment of clinical parameters including stage, LDH and metastatic spread.
Results
Median progression-free survival in pts with BMs was 6.1 months (CI 95% 5.2-6.9) vs 10.5 months (CI 95% 8.8-11.7) w/o BMs. The objective response rate (ORR) in pts with BMs was 31.9% while 3.3% achieved a complete response (CR). Pts w/o BMs had an ORR of 44.5% with 10.3% reaching a CR. Median duration of treatment was 6.3 months in pts with BMs and 7.0 months w/o BMs. 17% of pts w/o BMs had been assigned to slow tumor dynamics compared to 10% of pts with BMs; all other tumor dynamics subgroups were similar. Incidence rates of adverse events (AEs) were comparable with reported phase III data, although rates of common AEs, such as pyrexia, fatigue and skin-related toxicities, were lower.
Conclusions
The COMBI-r interim analysis provides evidence of the clinical benefit of D+T in pts with BRAFV600-mutated BMs. These real-world data are comparable to the phase II melanoma BMs trial COMBI-MB. Although AE rates were lower, the overall safety profile was consistent with previous phase III melanoma data. Nevertheless, the results illustrate the vast difference in clinical outcomes between melanoma pts with and w/o BMs underscoring the high medical need of this pt population.
Clinical trial identification
COMBI-r, non-Interventional Study.
Editorial acknowledgement
Legal entity responsible for the study
Novartis.
Funding
Novartis.
Disclosure
C. Berking: Honoraria (self), Research grant/Funding (institution): Amgen; Honoraria (institution), Research grant/Funding (institution): BMS; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Merck Serono; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution): Roche; Honoraria (self), Research grant/Funding (institution): 4SC; Research grant/Funding (institution): Array Pharma; Research grant/Funding (institution): Regeneron. D. Schadendorf: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Sanofi/Regeneron; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Array/Pfizer/Pierre Fabre; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche/Genentech; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Merck EMR; Advisory/Consultancy: Immunocore; Honoraria (institution), Advisory/Consultancy: Nektar; Honoraria (self), Advisory/Consultancy: 4SC. M. Weichenthal: Honoraria (self), Personal financial: Novartis; Honoraria (self), Personal financial: MSD; Honoraria (self), Personal financial: BMS; Honoraria (self), Personal financial: Roche; Honoraria (self), Personal financial: Sanofi; Honoraria (self), Personal financial: Pierre Fabre; Honoraria (self), Personal financial: Takeda; Honoraria (self), Personal financial: Sun Pharma. T. Eigentler: Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy: Leo Pharma; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD. P. Mohr: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses, Board membership: Amgen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, Board membership: BMS; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, Board membership: MSD; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses, Board membership: GSK; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses, Board membership: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses, Board membership: Merck; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses, Board membership: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses, Board membership: Sanofi; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses, Board membership: Pierre Fabre. K. Schober: Full/Part-time employment: Novartis Pharma GmbH. F. Kiecker: Advisory/Consultancy, Speaker Bureau/Expert testimony: Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Sanofi; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pierre Fabre. C. Loquai: Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck; Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pierre Fabre; Advisory/Consultancy, Speaker Bureau/Expert testimony: Sun Pharma. D. Debus: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pierre Fabre; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Sanofi. R. Gutzmer: Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Johnson&Johnson; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Amgen; Advisory/Consultancy, Research grant/Funding (institution): Merck Serono; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: GSK; Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Almirall-Hermal; Speaker Bureau/Expert testimony: Boehringer; Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Sun; Advisory/Consultancy: LEO; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Takeda; Advisory/Consultancy: 4SC; Advisory/Consultancy: Incyte. All other authors have declared no conflicts of interest.