BRAF-/MEK-Inhibition With Dabrafenib and Trametinib in Melanoma Patients

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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BRAF-/MEK-Inhibition With Dabrafenib and Trametinib in Melanoma Patients in the Adjuvant Setting: a Non-interventional Observatory Study

Conditions
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Melanoma

Intervention / Treatment
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* Drug: Dabrafenib and Trametinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with complete surgical resection of histologically confirmed AJCC (American Joint Committee on Cancer) (8th edition) clinical stage III (IIIA, IIIB, IIIC, IIID) melanoma, for whom a decision for adjuvant treatment with dabrafenib and trametinib has been made before entering the study. V600E/K mutation-positive cutaneous melanoma Adjuvant treatment with combination therapy of Dabrafenib (Tafinlar®) and Trametinib (Mekinist®) as indicated in the SmPC (Summary of Product Characteristics) and by prescription, that has been started no longer that 4 weeks before inclusion of the patient into the study or which will be initiated directly after inclusion Age ≥ 18 years Signed written informed consent Exclusion Criteria: Lack of basic demographics and staging information Current or planned participation within a clinical trial. The participation in a follow-up phase of a clinical trial without active intervention is allowed. Current or planned treatment of another tumor disease except keratoacanthoma, squamous cell or basal cell carcinoma of the skin

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Dabrafenib and Trametinib|Dabrafenib and trametinib treatment under routine conditions according to the applying SmPC.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median time on treatment | Median time on adjuvant dabrafenib + trametinib treatment defined as the interval between start of treatment and permanent discontinuation of treatment. | Date of first dose up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Permanent study drug discontinuation due to any reason | Rate of permanent study drug discontinuation due to any reason. | 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). | 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. | 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. | 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. | 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 | 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). | 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 | 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. | 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. | From date of first treatment until the date of treatment end, assessed up to 12 months | 
| Overall survival time | Overall survival (OS) time. | From date of first treatment until the date of treatment end, assessed up to 12 months | 
| Overall survival rate | Overall survival (OS) rate. | 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). | From date of first treatment until the date of treatment end, assessed up to 12 months |