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

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

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.

Study Overview

• Status: Completed
• Conditions: Malignant Melanoma
• Intervention / Treatment: Drug: dabrafenib + trametinib

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 3

Contacts and Locations

Study Locations

• Portugal
  • Center
    • Coimbra, Center, Portugal, 3000-075
      • Novartis Investigative Site
  • North
    • Oporto, North, Portugal, 4200-319
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients were recruited from participating centers in the routine setting. This was done only if the decision about starting treatment with darbafenib and trametinib has already been made. All patients that complied with the inclusion criteria and that start treatment with dabrafenib+ trametinib in the participating centers were considered to participate in the study, at investigator discretion.

Description

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).

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
dabrafenib + trametinib; Patients administered dabrafenib and trametinib	Drug: dabrafenib + trametinib; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2021
• Primary Completion (Actual): June 7, 2022
• Study Completion (Actual): June 7, 2022

Study Registration Dates

• First Submitted: September 8, 2020
• First Submitted That Met QC Criteria: September 8, 2020
• First Posted (Actual): September 14, 2020

Study Record Updates

• Last Update Posted (Actual): May 30, 2023
• Last Update Submitted That Met QC Criteria: May 26, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: adjuvant; Malignant melanoma; trametinib; dabrafenib; Mekinist; Tafinlar; FACT-M questionnaire; generic EQ-5D-3L questionnaire
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Trametinib; Dabrafenib
• Other Study ID Numbers: CTMT212APT02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No