Observational Study for Melanoma Adjuvant Treatment With Tafinlar® + Mekinist® (Dabrafenib + Trametinib)

Study Overview
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Brief Summary
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The primary objective for this non-interventional study was to assess the quality of life of melanoma patients under adjuvant treatment with dabrafenib and trametinib in real world setting in Portugal through disease specific FACT-M questionnaire and generic EQ-5D-3L questionnaire. The secondary study objectives were to assess the usage of adjuvant dabrafenib and trametinib in clinical practice and to evaluate clinical outcomes in patients that started adjuvant treatment with dabrafenib and trametinib. In addition, this study aimed to explore if treatment discontinuation affects clinical outcomes in real-world practice.

Detailed Description
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The prospective registration of completely resected high-risk stage III melanoma patients treated with dabrafenib and trametinib in the adjuvant setting was planned to be based on collaboration with 8 centers of excellence on melanoma patients treatment, according to their expertise and experience. Patients were recruited from participating centers in the routine setting. This was done only if the decision about starting treatment with dabrafenib and trametinib had already been made. All patients that complied with the inclusion criteria and that started treatment with dabrafenib+ trametinib during the recruitment period were considered to participate in the study, at investigator discretion. Health related quality of life had to be assessed by FACT-M and EQ-5D-3L questionnaires after treatment initiation in a quarterly base, according to clinical practice, including the first visit after treatment completion.

Official Title
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Impact of Melanoma Adjuvant Treatment With Tafinlar® + Mekinist® (Dabrafenib + Trametinib) on Patients Quality of Life (QoL) and Clinical Outcomes in Portuguese Real World Setting

Conditions
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Malignant Melanoma

Intervention / Treatment
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* Drug: dabrafenib + trametinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with complete surgical resection of histologically confirmed AJCC (8th edition) clinical stage III (IIIA, IIIB, IIIC, IIID) melanoma, in 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 and by prescription, that has been started before inclusion of the patient into the study; ≥ 18 years of age Written informed consent signed. Exclusion Criteria: Lack of basic demographic (gender, age, age at diagnosis) and staging data (Stage at diagnosis; Breslow index; Clark level; BRAF mutation; BRAF test date; Surgery date).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| dabrafenib + trametinib<br>Patients administered dabrafenib and trametinib | Drug: dabrafenib + trametinib<br>* There was no treatment allocation. Patients administered adjuvant treatment with combination therapy of Dabrafenib (Tafinlar®) and Trametinib (Mekinist®) by prescription that had started before inclusion of the patient into the study could be enrolled.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in FACT-M score | Health-related quality of life in melanoma patients defined as the mean difference in FACT-M (Functional Assessment of Cancer Therapy - Melanoma ) score. FACT-M is a specific version of FACT questionnaire validated for patients with any stage of melanoma and includes items related to physical, functional, social and emotional well-being, and specific concerns of melanoma patients and melanoma patients undergoing surgery. The FACT-M Total Score (FACT-M TS) ranges from 0 to 172. Higher scores represent a better quality of life. | Baseline, months 3-4, months 6-8, months 9-12, months 12, months 15-16 | 
| Change from baseline in EQ-5D-3L score | Health-related quality of life in melanoma patients defined as the mean difference in EQ-5D-3L score. EQ-5D-3L is a descriptive questionnaire comprising five dimensions regarding mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has three response levels of severity: no problems, some problems, extreme problems. The respondent was asked to indicate his/her health state by checking the box next to the most appropriate response level of each of the five dimensions. | Baseline, months 3-4, months 6-8, months 9-12, months 12, months 15-16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total duration of treatment | Total duration of treatment defined as median time on adjuvant treatment (from start to end of treatment/permanent treatment discontinuation). | months 12 | 
| Proportion of patients on treatment in each visit | Proportion of patients on treatment in each visit | Baseline, months 3-4, months 6-8, months 9-12, month 12 | 
| Rate of permanent study drug discontinuation due to any reason | Rate of permanent study drug discontinuation due to any reason. | month 12 | 
| Rate of permanent drug discontinuation due to pirexia | Rate of permanent drug discontinuation due to pirexia over the course of adjuvant treatment. | month 12 | 
| Rate of permanent drug discontinuation due to AEs | Rate of permanent drug discontinuation due to AEs over the course of adjuvant treatment | month 12 | 
| Reason of treatment discontinuation | Reason of treatment discontinuation (death, relapse, AEs, significant change in FACT-M, significant change in EQ-5D-3L , withdrawal of consent, other). | month 12 | 
| Average dose of dabrafenib and trametinib used during the treatment | Average dose of dabrafenib and trametinib used during the treatment, including dose reductions. | month 12 | 
| Proportion of patients who had dose reduction | Percentage of patients with dose reduction during treatment, and in this case, reason for dose reduction | month 12 | 
| Relapse Free Survival rate | RFS (Relapse Free Survival) | month 12 | 
| distant-metastasis-free survival rate | DMFS (distant-metastasis-free survival) rate | month 12 | 
| Overall Survival rate | OS (Overall Survival) rate | month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Malignant melanoma, Tafinlar, Mekinist, dabrafenib, trametinib, FACT-M questionnaire, generic EQ-5D-3L questionnaire, adjuvant