Abstract 1075P
Background
The 5-y analysis of the Phase III COMBI-AD trial (NCT01682083) showed long-term RFS benefit with 12 months of adjuvant dabrafenib (dab) plus trametinib (tram) vs placebo (pbo) in patients with resected stage III BRAF V600E/K–mutant melanoma (5-y RFS rate, 52% vs 36%; hazard ratio, 0.51 [95% CI, 0.42-0.61]). A prior regression tree analysis (median follow-up in the dab + tram arm, 44 mo) evaluated 13 patient and clinical characteristics to identify treatment type (dab + tram vs pbo), disease stage, and age as predictive of long-term benefit. We present an updated model that is based on the 5-y RFS data and incorporates additional variables.
Methods
This updated regression tree analysis (median follow-up, 60 mo) is evaluating baseline demographics, clinical characteristics, and biomarker parameters as candidate predictors for classification of patients enrolled in COMBI-AD (N = 870) into subgroups based on similar RFS. Patient and clinical characteristics included are age, sex, geographical region, BRAF V600 mutation type, body mass index, histological subgroup, T stage, N stage, number of positive lymph nodes, ulceration status, lactate dehydrogenase level, Eastern Cooperative Oncology Group performance status, time to treatment initiation, and treatment type. Biomarkers will include tumour mutational burden/landscape and gene expression signatures in baseline tissue samples generated by sequencing 570 genes and gene expression profiling with a NanoString® panel, respectively.
Results
A preliminary tree incorporating patient and clinical characteristics identified treatment type (dab + tram vs pbo), N stage, and T stage as important variables defining 5-y RFS subgroups. Evaluation of biomarkers for inclusion in the model is ongoing. Further refinements, including stability and goodness-of-fit analyses, are also in progress; the final tree will be presented.
Conclusions
These findings confirm and extend previous results using regression tree analysis to identify subgroups that may particularly benefit from adjuvant therapy. Such analyses may inform treatment decisions.
Clinical trial identification
NCT01682083.
Editorial acknowledgement
Medical writing assistance was provided by Amy Ghiretti, PhD (ArticulateScience LLC), and was funded by Novartis Pharmaceuticals Corporation.
Legal entity responsible for the study
Novartis.
Funding
Novartis.
Disclosure
C. Robert: Financial Interests, Personal, Advisory Role: BMS, Roche, Pierre Fabre, Novartis, Amgen, Sanofi, Merck, MSD, AstraZeneca. M.A. Davies: Financial Interests, Personal, Research Grant: Nanostring; Financial Interests, Personal, Other, Consulting fees: Novartis, Roche/Genentech, Array, Pfizer, BMS, Vaccinex, Apexigen, ABM Therapeutics . R. Dummer: Financial Interests, Personal, Other, Honoraria: Novartis, MSD, BMS, Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, Alligator, MaxiVAX SA, touchIME; Financial Interests, Personal, Other, Consulting fees: Novartis, MSD, BMS, Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, Alligator, MaxiVAX SA, touchIME. J.J. Grob: Financial Interests, Personal, Other, Consultancy fees: Roche, Novartis, BMS, MSD, Amgen, Pierre Fabre, Sanofi, Merck, Pfizer; Financial Interests, Personal, Other, Honoraria: Roche, Novartis, BMS, MSD, Amgen, Pierre Fabre, Sanofi, Merck, Pfizer; Financial Interests, Personal, Other, Attending meetings & travel: Roche, Novartis, BMS, MSD, Pierre Fabre,. A. Hauschild: Financial Interests, Institutional, Research Grant: Amgen, BMS, Merck, Pfizer, Philogen, Pierre Fabre, Regeneron, Roche, Sanofi-Genzyme, Novartis, Eisai, Immunocore, Replimune, Seagen; Financial Interests, Personal, Other, Consulting fees: Merck, Philogen, Pierre Fabre, Regeneron, Roche, Sanofi-Genzyme, Novartis, Eisai; Financial Interests, Personal, Other, Speaker honoraria: Amgen, BMS, Merck, Pfizer, Pierre Fabre, Regeneron, Roche, Sanofi-Genzyme, Novartis, Eisai; Financial Interests, Personal, Other, Attending meetings and/or travel: Amgen, BMS, Merck, Pfizer, Philogen, Pierre Fabre, Regeneron, Roche, Sanofi-Genzyme, Novartis, Eisal; Financial Interests, Personal, Advisory Board: BMS, Merck, Pfizer, Pierre Fabre, Regeneron, Roche, Sanofi-Genzyme, Novartis, Eisai, Immunocore, Replimune, Seagen. J.M. Kirkwood: Financial Interests, Personal, Advisory Role: BMS, Novartis, Iovance, Elsevier, Amgen, Checkmate, Harbour BioMed, Istari Oncology, Oncosec, Scopus BioPharma, Pfizer, Oncocyte, Takeda, AXIO Research, Immunocore, Natera Inc., DermTech; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Institutional, Research Grant: Amgen, BMS, Castle Biosciences, Checkmate, Immunocore, Iovance, Novartis, Merck. G.V. Long: Financial Interests, Personal, Advisory Role: Aduro Biotech Inc, Amgen Inc, Array Biopharma inc, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Hexel AG, Highlight Therapeutics S.L., Merck Sharpe & Dohme, Novartis Pharma AG, OncoSec, Pierre Fabre, QBiotics Group Limited, Regeneron Pha; Financial Interests, Personal, Invited Speaker: BMS, Pierre Fabre; Financial Interests, Personal, Advisory Board: Aduro Biotech Inc, Amgen Inc, Array Biopharma inc, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Hexel AG, Highlight Therapeutics S.L., Merck Sharpe & Dohme, Novartis Pharma AG, OncoSec, Pierre Fabre, QBiotics Group Limited, Regeneron Pha. P.D. Nathan: Financial Interests, Personal, Advisory Role: AZ, BMS, Immunocore, Ipsen, MSD, Merck, Novartis, Pfizer, 4SC; Financial Interests, Personal, Other, Honoraria: Novartis, Merck, Pfizer; Financial Interests, Personal, Other, Attending meetings & travel: BMS. H. Banerjee: Financial Interests, Personal, Stocks/Shares: BMS; Financial Interests, Personal, Full or part-time Employment: Novartis. B.G. Sahoo: Financial Interests, Personal, Full or part-time Employment: Novartis. M. Lau: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. K. Biette: Financial Interests, Personal, Full or part-time Employment: Novartis. A.D. Boran: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. D. Schadendorf: Financial Interests, Institutional, Funding, Case money for conducting the study to institution: Novartis; Financial Interests, Institutional, Research Grant: Novartis, BMS and Amgen; Financial Interests, Personal, Advisory Role: Novartis, BMS, MSD, Roche, Incyte, Array, Pierre Fabre, Pfizer, Sanofi-Genzyme, Regeneron, 4SC, InFlarX, Neracare, Ultimovacs, Sun Pharma, Philogen, Amgen, Merck-Serono, Immunocore, Sandoz-Hexal; Financial Interests, Personal, Other, Honoraria: Novartis, BMS, Pierre Fabre, Sanofi-Genzyme, Merck-Serono; Financial Interests, Personal, Other, Attending meetings and travel: Novartis, BMS, MSD, Roche, Incyte, Array, Pierre Fabre, Pfizer, Sanofi-Genzyme, Regeneron, 4SC, InFlarX, Neracare, Ultimovacs, Sun Pharma, Philogen, Amgen, Merck-Serono, Immunocore, Sandoz-Hexal; Financial Interests, Personal, Advisory Board: Novartis, BMS, MSD, Roche, Incyte, Array, Pierre Fabre, Pfizer, Sanofi-Genzyme, Regeneron, 4SC, InFlarX, Neracare, Ultimovacs, Sun Pharma, Philogen, Amgen, Merck-Serono, Immunocore, Sandoz-Hexal; Financial Interests, Personal, Leadership Role: Dermatologic Cooperative Oncology Group (DeCOG), German Cancer Society, Hilfe-Stiftung, Deutsche Hautkrebsstiftung, NVKH eV, EuMelaReg. All other authors have declared no conflicts of interest.