Retrospective analysis of safety in elderly metastatic or unresectable BRAF V600 melanoma patients treated with Tafinlar (dabrafenib) plus Mekinist (trametinib) and correlation with clinical features and non-elderly patients

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Drug utilisation

  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Other
• Non-interventional study design, other:
  Retrospective study

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  DABRAFENIB

  TRAMETINIB
• Medical condition to be studied:
  Malignant melanoma

Population studied

• Short description of the study population:
  The study population have been adult patients with metastatic or unresectable BRAF V600 melanoma, who have received at least one dose of dabrafenib combined with trametinib or dabrafenib monotherapy (in case that combination treatment was available and monotherapy was considered a medical decision).; Criteria for inclusion: Patients will be included in the study if all of the following criteria are met:; 1. Age≥ 18 years old; 2. Stage IIIC unresectable or stage IV melanoma with BRAF V600 mutation; 3. Treatment with at least one dose of dabrafenib plus trametinib, or with dabrafenib monotherapy due to clinician decision (safety, contraindications, etc.) at one of the participating study sites. Patients treated in a compassionate use program are eligible following local regulation.; 4. Written informed consent following local regulation (if the patient is alive). If the effort to obtain the informed consent is beyond that is reasonable and feasible, then Ethics Independent Committees (EICs) approval must be obtained (as established in local the regulation Orden SAS 3470/2009).; 5. Available medical records; Criteria for exclusion: Patients are excluded from participating in this study if one or more of the following criteria are met:; 1. Patients treated with dabrafenib monotherapy before trametinib was available (June 2013).
• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Special population of interest:
  Other
• Special population of interest, other:
  Malignant melanoma patients
• Estimated number of subjects:
  205

Study design details

• Main study objective:
  The primary objective of the study is to describe safety and real-world management of abrafenib and trametinib in the elderly (? 75 years old) Spanish population.
• Outcomes:
  Safety measures and endpoints are as follows, and should be provided in the analysis for patients <75 y.o. and ? 75 y.o. (primary endpoint) separately:- occurrence and intensity (grade CTC-AE v4.03) of adverse events- dose delays, dose adjustments, or treatment discontinuation for the management of adverse events. Secondary efficacy measures and endpoints should be provided in the analysis for patients<75 y.o. and ? 75 y.o.:-Response rate by RECIST (v1.1)-Progression-free survival-Overall survivalDemographics/clinical characteristics: age, sex, stage of disease, metastatic disease, comorbidities, concomitant medications, ECOG and LDH. Real-world management: line of treatment, discontinuation, etc
• Data analysis plan:
  This study is descriptive in nature and no formal hypotheses will be tested. The first step in the evaluation of the data will be to use standard exploratory and descriptive analyses to gain and understanding of the qualitative and quantitative nature of the data collected and of the characteristics of the sample studied. All data collected and endpoints will be summarized using descriptive statistics in addition to statistical modeling. Absolute and relative frequency distributions of qualitative variables will be presented, as well as mean, standard deviation, median, minimum and maximum valuesof quantitative ones. Ninety-five percent (95%) confidence intervals (CI) will be presented for the main quantitative variables When an inferential analysis is required, parametric tests will be used for continuous variables and nonparametric tests in the case of ordinal or categoricalor nonparametric variables. All hypothesis tests will be two-sided and with a significance level of 0.05.

Documents

Study results

CDRB436BES04_CSR FINAL V17Jul2020_Redacted