Adjuvant therapy with dabrafenib plus trametinib in melanoma was approved in 2018 by the EMA (EUropean Medicines Agency). The purpose of this non-interventional study is to assess the usage of adjuvant dabrafenib and trametinib in clinical practice, where the patient population may differ from study population.
Melanoma is a disease of significant metastatic potential if not detected very early. Oncogenic mutations in BRAF (B-Raf proto-oncogene, serine/threonine kinase) are found in approximately 40% of melanomas and result in constitutive activation of the MAPK (Mitogen-Activated Protein Kinase) pathway. Treatment with the BRAF inhibitor dabrafenib plus the MEK (Mitogen-activated protein kinase kinase) inhibitor trametinib showed improved overall survival in patients with unresectable or metastatic BRAF V600E/K-mutant melanoma (COMBI-d and COMBI-v studies). In an adjuvant setting treatment with dabrafenib and trametinib significantly reduced the risk of melanoma recurrence in patients with high-risk, stage III BRAF V600-mutant melanoma, with improvements in OS (Overall Survival), DMFS (Distant Metastasis Free Survival), and FFR (Freedom From Relaps) (COMBI-AD study). Based on these results, adjuvant dabrafenib plus trametinib therapy was approved in 2018 by the EMA. Compared to the metastatic situation, issues of compliance and treatment adherence may be more relevant in adjuvant treatments, as patients are free of disease and potentially cured even without adjuvant treatment. As the routine administration of drugs including dosing, treatment interruptions, and early termination in clinical practice may vary from procedures defined in clinical trials, this study aims to assess the usage of adjuvant dabrafenib and trametinib in the routine clinical setting.
Study Type
OBSERVATIONAL
Enrollment
232
Dabrafenib and trametinib treatment under routine conditions according to the applying SmPC.
Median time on treatment
Median time on adjuvant dabrafenib + trametinib treatment defined as the interval between start of treatment and permanent discontinuation of treatment.
Time frame: Date of first dose up to 12 months
Permanent study drug discontinuation due to any reason
Rate of permanent study drug discontinuation due to any reason.
Time frame: From date of first treatment until the date of treatment end, assessed up to 12 months
Permanent study drug discontinuation due to adverse drug reactions
Rate of permanent study drug discontinuation due to adverse drug reactions (ADRs).
Time frame: From date of first treatment until the date of treatment end, assessed up to 12 months
Pyrexia and related symptoms
Occurrence of pyrexia and related symptoms, listing the grade, number of episodes, and time to resolution.
Time frame: From date of first treatment until the date of treatment end, assessed up to 12 months
Adverse drug reaction management: pyrexia
Type of adverse drug reaction (ADR) management applied for pyrexia and correlation with occurrence/persistence of pyrexia.
Time frame: From date of first treatment until the date of treatment end, assessed up to 12 months
Adverse drug reactions in Follow-up
ADRs persisting/emerging up to 3 months post-treatment.
Time frame: From date of first treatment until the date of treatment end plus 3 months of follow-up, assessed up to 15 months
Health-related quality of life
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Elbe Kliniken Stade - Buxtehude GmbH
Buxtehude, Lower Saxony, Germany
Universitätsklinikum Essen, Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
Essen, North Rhine-Westphalia, Germany
Universitätsklinik Kiel, Klinik für Dermatologie, Venerologie und Allergologie
Kiel, Schleswig-Holstein, Germany
Katholisches Klinikum Bochum
Bochum, Germany
Klinikum Bremen Mitte gGmbH
Bremen, Germany
Klinikum Bremerhaven Reinkenheide gGmbH
Bremerhaven, Germany
DRK Krankenhaus Chemnitz Rabenstein
Chemnitz, Germany
Klinikum Darmstadt GmbH
Darmstadt, Germany
Klinikum Dortmund gGmbH
Dortmund, Germany
Krankenhaus Dresden-Friedrichstadt
Dresden, Germany
...and 26 more locations
Assessment of health-related quality of life (HRQoL), measured by the European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC-QLQ-C30). The EORTC QLQ-C30 consists of the folowing scales, with each dimension specifying five levels of severity \[not at all (level 1), a little (level 2), quite a bit (level 3), very much (level 4)\]: * functional scales (Physical, Role, Cognitive, Emotional, Social Functioning) * symptom scales (Fatigue, Pain and Nausea/Vomiting) * single item scales (Dyspnoea, Insomnia, Appetite Loss, Constipation, Diarrhoea and Financial Difficulties). Additionally the Global Health Status and QoL scales are incorporated, specifying on a scale from 1 (very poor) to 7 (excellent).
Time frame: Over the course of treatment plus 3 months safety follow up, assessed up to 15 months
Relapse free survival
Relapse free survival (RFS) time and rate
Time frame: From date of first treatment until the date of treatment end, assessed up to 12 months
Distant metastasis free survival time
Distant metastasis free survival (DMFS) time.
Time frame: From date of first treatment until the date of treatment end, assessed up to 12 months
Distant metastasis free survival rate
Distant metastasis free survival (DMFS) rate.
Time frame: From date of first treatment until the date of treatment end, assessed up to 12 months
Overall survival time
Overall survival (OS) time.
Time frame: From date of first treatment until the date of treatment end, assessed up to 12 months
Overall survival rate
Overall survival (OS) rate.
Time frame: From date of first treatment until the date of treatment end, assessed up to 12 months
Time on treatment and efficacy endpoints
Correlation between time on treatment and efficacy endpoints (RFS, DMFS, OS).
Time frame: From date of first treatment until the date of treatment end, assessed up to 12 months