1099P - COMBI-EU: Adverse event management of adjuvant dabrafenib plus trametinib (D+T) in patients with BRAF V600-mutant melanoma

Background

The COMBI-AD study showed that adjuvant therapy with D+T significantly reduces recurrence risk in resected stage III BRAF V600–mutant melanoma patients (pts), leading to its EMA approval in 2018. In the study, 26.2% pts discontinued treatment (tx) due to adverse events (AE). The COMBI-APlus trial hypothesised that better AE management could improve tx adherence. The COMBI-EU is a prospective, non-interventional study which aims to assess the usage of adjuvant D+T in clinical practice, and the impact of AE management and usage of app-based documentation on tx adherence.

Methods

This study included adults with complete surgical resection of stage III BRAF V600-mutant cutaneous melanoma. AE management was classified as either high or low level of management based on published guidelines. Impact of AE management on time on tx was analysed by a self-developed algorithm and an adapted algorithm from COMBI-APlus. Usage of an app-based documentation of medication intake (Cankado PRO-React) was offered to pts and health-related quality of life was evaluated via the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).

Results

Of 225 pts, 138 (61.3%) completed tx and 37 (16.4%) discontinued due to tx-related AEs. At least 1 tx-related AE occurred in 181 pts (80.4%), pyrexia being the most common (38.2%). High-level AE management improved tx adherence (high level vs. low level: hazard ratio [HR]: 0.74 (95% confidence interval [CI] 0.49-1.14), this improvement was particularly notable with pyrexia management (HR: 0.52 [95% CI 0.29-0.93]). Only 79 of 225 pts intended to use the electronic app during the study. Age was a significant factor discriminating app users from app non-users (53.4 (14.0) vs. 59.0 (13.9) years). A similar proportion of pts remained on tx for 12 months with or without app usage (39.4% vs 36.5%).

Conclusions

High level AE management, particularly for pyrexia, correlated with improved tx adherence in resected BRAF V600-mutant melanoma pts treated with adjuvant D+T. The optional use of an app did not impact tx adherence. Further research is important to understand the impact of tx adherence for the effectiveness of adjuvant tx.

Clinical trial identification

NCT03944356.

Editorial acknowledgement

Medical writing assistance was provided by Emma Richards-Sirianni, PhD, Novartis UK Ltd.

Legal entity responsible for the study

Novartis AG.

Funding

Novartis AG.

Disclosure

P. Mohr: Financial Interests, Personal, Other, Honoraria: MSD, Novartis, Bristol Myers Squibb, Pierre Fabre, Sanofi Genzyme, Immunocore, Almirall Hermal, Sun Pharma; Financial Interests, Personal, Other, Attending meetings and/or travel: MSD, Bristol Myers Squibb, Sun Pharma, Novartis; Financial Interests, Personal, Advisory Board, Or Data Safety Monitoring Board: Novartis, Bristol Myers Squibbs, Pierre Fabre, Sanofi Genzyme, Beiersdorf, Regeneron, Sun Pharma, BioNTech; Financial Interests, Personal, Leadership Role, Unpaid: Melanom Info Deutschland, Hautkrebs Netzwerk Deutschland. D. Debus: Financial Interests, Personal, Advisory Board: MSD, BMS, Sanofi, Novartis, Pierre Fabre, Kyowa Kirin, SUN; Financial Interests, Personal, Principal Investigator: MSD, BMS, Sanofi, Novartis, Pierre Fabre, Pfizer; Financial Interests, Personal, Other, Travel support, conference fees: Pfizer, Boehringer Ingelheim Ingelheim, Celltrion; Financial Interests, Personal, Other, Role as sub-investigator: BioNTech, Regeneron; Financial Interests, Personal, Other, Role as sub investigator: Boehringer Ingelheim Ingelheim; Financial Interests, Institutional, Other, Study site: BMS, Sanofi, Novartis, Pierre Fabre, BioNTech, Pfizer, Regeneron. I. von Wasielewski: Financial Interests, Personal, Advisory Board: BMS, MSD, Sanofi; Financial Interests, Personal, Invited Speaker: Stemline, Kyowa Kirin; Financial Interests, Personal, Other, Travel und Accomodation assist: Pierre Fabre. C. Gebhardt: Financial Interests, Personal, Advisory Board, And/or has received honoraria: Almirall, Amgen, Beiersdorf, BioNTech, Bristol Myers Squibb, Immunocore, Janssen, MSD, Novartis, Pierre Fabre, Regeneron, Roche, Sanofi Genzyme, Sun Pharma, Sysmex; Financial Interests, Personal, Funding, Research: Bristol Myers Squibb, Novartis, Regeneron, Sanofi; Financial Interests, Personal, Other, Co-founder: Dermagnostix and Dermagnostix R&D. M.V. Heppt: Financial Interests, Personal, Other, Honoraria: MSD, Bristol Myers Squibb, Roche, Novartis, Sun Pharma, Sanofi, Almirall, Biofrontera, Galderma. J.C. Hassel: Financial Interests, Personal, Other, Speaker honoraria: Amgen, Bristol Myers Squibb, Delcath, Novartis, Pierre Fabre, Sanofi, Sun Pharma, GSK, Immunocore, MSD; Financial Interests, Personal, Advisory Board, Honoraria: GSK, Pierre Fabre, Sun Pharma; Financial Interests, Personal, Other, Travel support: Bristol Myers Squibb, Iovance Biotherapeutics, Sun Pharma; Financial Interests, Institutional, Funding, Grant: Bristol Myers Squibb, Sanofi, Sun Pharma. F. Ziller: Financial Interests, Personal, Advisory Board, And/or travel support: Bristol Myers Squibb, MSD, Roche, Novartis, Pierre Fabre, Sanofi, Sun Pharma. M. Weichenthal: Financial Interests, Institutional, Funding: Merck Sharp & Dohme, Bristol Myers Squibb, Novartis, 4SC, Innate Pharma; Financial Interests, Personal, Other, Honoraria: Merck Sharp & Dohme, Roche, Novartis, Bristol Myers Squibb, Sanofi; Financial Interests, Personal, Advisory Role: Sun Pharma, Sanofi, Pierre Fabre, Merck Sharp & Dohme, Roche, Novartis, Bristol Myers Squibb. M. Aoun: Financial Interests, Personal, Full or part-time Employment, Full-time employee: Novartis. G. Schley: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Other, Lecture: Kyowa Kirin. J. Ulrich: Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb, Pierre Fabre, Sanofi Genzyme, Sun Pharma; Financial Interests, Personal, Other, Attending meetings and/or travel: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, Or on a Data Safety Monitoring Board: Bristol Myers Squibb, Sun Pharma. J. Utikal: Financial Interests, Personal, Advisory Board, And/or honoraria/travel support: Immunocore, Rheacell. F. Meier: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Immunocore, MSD, Novartis, Philogen, Sanofi; Financial Interests, Personal, Invited Speaker: Immunocore, Sanofi. P. Terheyden: Financial Interests, Personal, Other, Travel support: Bristol Myers Squibb, Pierre Fabre; Financial Interests, Personal, Other, Consulting fees/honoraria: Almirall, Biotest, Biofrontera, Bristol Myers Squibb, Kyowa Kirin, 4SC, Sanofi. R. Gutzmer: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Pierre Fabre, Novartis, MSD, Merck Serono, Almirall, Immunocore, Delcath, KyowaKirin, Sanofi/Regeneron, SUN Pharma; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Pierre Fabre, Novartis, MSD, Merck Serono, Almirall, Sanofi/Regeneron, SUN Pharma; Financial Interests, Institutional, Research Grant: KyowaKirin, Almirall, SUN Pharma, Amgen, Sanofi/Regeneron, Merck Serono; Non-Financial Interests, Member of Board of Directors: DeCOG; Other, Other, Travel and meeting support: Pierre Fabre, SUN Pharma. D. Schadendorf: Financial Interests, Personal, Invited Speaker: BMS, MSD, Merck Serono, Sanofi, Neracare, SunPharma; Financial Interests, Personal, Advisory Board: BMS, Novartis, MSD, Immunocore, Pierre Fabre, Sanofi/Regeneron, Pfizer, Philogen, Neracare, InFlarX, BioAlta, Daiichi Sanyko, NoviGenix, Anaveon, AstraZeneca, PamGene, BioNTech, Immatics, CureVac, Erasca, Formycon, Replimune, Seagen, SunPharma, Ultimovacs; Financial Interests, Personal, Steering Committee Member: Novartis, BMS, MSD; Financial Interests, Institutional, Coordinating PI: Novartis, BMS, MSD, Pierre Fabre; Financial Interests, Institutional, Research Grant: BMS, MSD; Financial Interests, Institutional, Local PI: Sanofi, Philogen; Non-Financial Interests, Member of Board of Directors: EORTC-MG; Non-Financial Interests, Leadership Role, Founding member and SC chair: European Melanoma Registry (EuMelaReg). All other authors have declared no conflicts of interest.