Abstract 828P
Background
Targeted therapies (TT) with BRAF/MEK inhibitors and immunotherapy (anti-PD-1 ± anti-CTLA-4 antibodies) have shown significant improvements of outcomes in patients (pts) with BRAFV600 mutated metastatic melanoma (mM) and are used routinely in clinical practice. However, real-world data is still limited, especially regarding effectiveness of TT in different therapy lines and subgroups that are usually excluded in phase III clinical trials, e.g. pts with brain metastases (BM). Therefore, the objective of the prospective non-interventional COMBI-r study was to assess the treatment of mM pts with dabrafenib and trametinib (D+T) regarding effectiveness across different therapy lines and subgroups.
Methods
In total, 504 pts at 55 German Skin Cancer Centers were enrolled in COMBI-r between Dec 2015 and Dec 2018. Following inclusion and exclusion criteria, 472 pts were included in the final analysis. During the first year on treatment, visits were scheduled every 3 months (mo), followed by half-yearly visits until the end of treatment (EoT), and two follow-up visits at 3 and 6 mo after EoT.
Results
95.3% pts of the final analysis population entered the follow-up phase, while 81.4% pts suffered a progression and 56.1% died. Overall survival (OS) and progression-free survival (PFS) were analyzed by line of therapy (1L, 2L, ≥3L) with D+T. Outcomes were correlated with baseline demographics and clinical, laboratory and biological parameters, i.e., tumor dynamics, BM, elevated LDH, and ≥3 metastatic sites. Between therapy lines, no differences in BM development were observed and median PFS as well as median OS were comparable. Table: 828P
| 1L | 2L | ≥3L | Total | |
| Median PFS [mo (95% CI)] | 7.7 (6.6-9.1) | 10.3 (7-11.8) | 8.3 (6.3-11.4) | 8.3 (7.1-9.3) |
| Median OS [mo (95% CI)] | 17.5 (13.3-21.3) | 20.2 (12-n/a) | 19.8 (13.7-35.6) | 18.3 (14.9-21.3) |
Conclusions
Data from COMBI-r shed light on the real-world situation of mM pts treated with D+T and describe clinical outcomes stratified by established predictive factors. The final analysis points to D+T as an effective treatment strategy even in higher therapy lines for mM pts.
Clinical trial identification
Registry: Germany BfArM Registration Number: NIS 6690.
Editorial acknowledgement
Legal entity responsible for the study
Novartis Pharma GmbH.
Funding
Novartis Pharma GmbH.
Disclosure
C. Berking: Non-Financial Interests, Personal, Leadership Role: DeCOG/ADO, Hiege Foundation against skin cancer, NVKH e.V. (Skin Cancer Council Germany); Financial Interests, Personal, Other, Travel support to visit scientific conferences: BMS, MSD, Amgen, Pierre Fabre; Financial Interests, Personal, Other, Speaker, consultancy and/or advisory role or similar activity: Roche, BMS, MSD, Novartis, Amgen, Merck Serono, Almirall, Sun Pharma, Sanofi, Pierre-Fabre, 4SC, Immunocore, Leo Pharma, Regeneron; Financial Interests, Institutional, Sponsor/Funding, Clinical traisl/contracted research: BMS, Sanofi, Almirall, CureVac, Pfizer, Novartis, Merck Serono, Pierre-Fabre, MSD, Roche, Leo Pharma, 4SC, InflaRx, Immunocore, Roche. E. Livingstone: Financial Interests, Other, Consultant and/or honorarium: BMS, MSD, Medac, Novartis, Pierre Fabre, Recordati, Sanofi, Sunpharma; Financial Interests, Other, Travel support: BMS, MSD, Novartis, Pierre Fabre, Sunpharma. M. Weichenthal: Financial Interests, Research Grant: Novartis, MSD, Millenium; Financial Interests, Advisory Role: Sanofi, MSD, BMS, Novartis, Sunpharma; Financial Interests, Invited Speaker: Medac; Financial Interests, Other, Travel support/attending meetings: Novartis, Pierre Fabre, MSD; Financial Interests, Advisory Board: Roche, MSD, Novartis. U. Leiter-Stoppke: Financial Interests, Research Grant: MSD; Financial Interests, Invited Speaker: Roche, Novartis, Sanofi, MSD; Financial Interests, Advisory Role: Roche, Sanofi, MSD, Novartis. J. Remy: Financial Interests, Personal, Full or part-time Employment: Novartis Pharma GmbH. T. Eigentler: Financial Interests, Personal, Advisory Board: BMS, Novartis, Pierre Fabre, Sanofi, Immunogenics. P. Mohr: Financial Interests, Institutional, Research Grant: BMS, MSD, Novartis; Financial Interests, Personal, Invited Speaker: Roche, BMS, Novartis, MSD, Almirall-Hermal, Amgen, Merck Serono, Bayer, Pierre Fabre, Sanofi; Financial Interests, Personal, Advisory Board: Bayersdorf, Roche, BMS, Novartis, MSD, Almirall-Hermal, Amgen, Pierre Fabre, Merck Serono, SUN, Sanofi. C. Loquai: Financial Interests, Advisory Board: Novartis, Pierre Fabre, BMS, Roche, Biontech, Sun Pharma, MSD, Merck, Sanofi, Immunocore, Almirall Hermal, Kyowa Kirin; Financial Interests, Invited Speaker: Novartis, Pierre Fabre, BMS, Roche, Biontech, Sun Pharma, MSD, Merck, Sanofi, Immunocore, Almirall Hermal, Kyowa Kirin; Financial Interests, Other, Travel reimbursement: Novartis, Pierre Fabre, BMS, Roche, Biontech, Sun Pharma, MSD, Merck, Sanofi, Immunocore, Almirall Hermal, Kyowa Kirin. D. Debus: Financial Interests, Personal, Advisory Role: BMS, MSD, Novartis, Pierre Fabre, Roche, Sanofi; Financial Interests, Personal, Other, Honoraria: BMS, Kyowa Kirin, MSD, Novartis, Pierre Fabre, Roche, Sanofi, Amgen; Financial Interests, Personal, Other, Travel, Accomodations, Expenses: BMS, MSD, Mylan, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi. R. Gutzmer: Financial Interests, Personal, Other, Speaker, consultancy and/or advisory role or similar activity: Roche, BMS, MSD, Novartis, Amgen, Merck Serono, Almirall, SUN, Sanofi, Pierre Fabre, 4SC, Immunocore; Financial Interests, Personal, Project Lead: Johnson&Johnson, Amgen, Merck Serono, Sanofi, Kyowa Kirin, Almirall; Financial Interests, Institutional, Sponsor/Funding, Clinical trials or contracted research: BMS, Sanofi, SUN, IO Biotech, Pfizer, Novartis, Merck Serono, Pierre Fabre, MSD; Non-Financial Interests, Personal, Leadership Role: DeCOG/ADO; Financial Interests, Other, Travel support for meeting participation: Roche, BMS, SUN, Merck Serono, Pierre Fabre. All other authors have declared no conflicts of interest.