A Multi-center Retrospective Study With Secondary Use of Data of Tafinlar (Dabrafenib) Plus Mekinist (Trametinib) in Chinese Patients With BRAF V600 Mutation Positive Melanoma

This was a multi-center, observational, retrospective cohort study to evaluate the effectiveness and safety of dabrafenib in combination with trametinib in Chinese patients with unresectable or metastatic BRAF V600 mutation positive melanoma, for mucosal melanoma patients (Cohort A) and non-mucosal melanoma patients (Cohort B, cutaneous and acral melanoma), separately. Study population was identified as patients initiating dabrafenib plus trametinib from 01 May 2020 to 31 July 2022 who fulfilled the inclusion/exclusion criteria. The follow-up period ended at the earliest of the following: end of study observation period (i.e., 31 December 2022), death, upon withdrawal of consent or the last available record.

Study Overview

• Status: Completed
• Conditions: BRAF V600 Mutation Positive Melanoma

• Study Type: Observational
• Enrollment (Actual): 90

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 201203
    • Novartis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This was a retrospective, noninterventional cohort study.

Description

Inclusion Criteria:

Cohorts A and B:

• Initiated dabrafenib and trametinib combination therapy (D+T) according to approved label between 01 May 2020 and 31 July 2022
• Was ≥18 years old of age at the initiation of D+T
• Had at least one tumor assessment after initiation of D+T
• Written informed consent if requested by the study site

Cohort A Only • Confirmed BRAF V600 mutation positive mucosal melanoma that was unresectable or metastatic

Cohort B Only

• Confirmed BRAF V600 mutation positive non-mucosal melanoma (cutaneous and acral melanoma) that was unresectable or metastatic

Exclusion Criteria:

None specified

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Cohort A (mucosal melanoma patients)
Cohort B (non-mucosal melanoma patients)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Real-world overall response rate (rwORR)	ORR was defined as the percentage of patients demonstrating a best overall response as complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or as documented per physician assessment, as available.	Up to approximately 2.6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Age		Baseline
Percentage of patients per sex		Baseline
Number of years of disease history at treatment initiation since initial melanoma diagnosis		Baseline
Number and percentage of patients per anatomic sites of origin		Baseline
Number of years of disease history at treatment initiation since unresectable or metastatic melanoma diagnosis		Baseline
Number and percentage of patients per tumor stage		Baseline
Number and percentage of patients with occurrence of tumor metastasis		Baseline
Number and percentage of patients per metastatic location		Baseline
Number and percentage of patients per metastases		Baseline
Lactate dehydrogenase (LDH) levels		Baseline
Eastern Cooperative Oncology Group (ECOG) performance status	ECOG performance status describes a patient's level of functioning in terms of their ability to care for themself, daily activity, and physical ability (walking, working, etc.). Scores can range from a lower value of 0 (fully active, able to carry on all pre-disease performance without restriction) up to 5 (dead).	Baseline
Number and percentage of patients who had at least one surgery for melanoma prior to D+T treatment		Baseline
Number and percentage of patients per type of surgery		Baseline
Number and percentage of patients per name of surgery		Baseline
Number and percentage of patients per surgical and medical procedure		Baseline
Number and percentage of patients who had at least one anti-neoplastic drug for melanoma prior to D+T treatment		Baseline
Number and percentage of patients with prior anti-neoplastic drugs for melanoma per treatment intent		Baseline
Number and percentage of patients with prior anti-neoplastic drug for melanoma per treatment setting		Baseline
Number and percentage of patients with prior anti-neoplastic drug for melanoma per line of treatment		Baseline
Number and percentage of patients with prior anti-neoplastic drug for melanoma per treatment type		Baseline
Number and percentage of patients per reason for immunotherapy discontinuation		Baseline
Number and percentage of patients with prior anti-neoplastic drug for melanoma with best overall tumor response		Baseline
Number and percentage of patients per prior anti-neoplastic drug for melanoma		Baseline
Number and percentage of patients who had at least one radiotherapy for melanoma prior to D+T treatment		Baseline
Number and percentage of patients with prior radiotherapy for melanoma per treatment intent		Baseline
Number and percentage of patients with prior radiotherapy for melanoma per treatment setting		Baseline
Number and percentage of patients per radiation site		Baseline
Mean total dosage for all radiotherapy		Baseline
Number and percentage of patients with prior radiotherapy for melanoma with best overall tumor response		Baseline
Number and percentage of patients with dabrafenib plus trametinib treatment per line of treatment		Up to approximately 2.2 years
Number and percentage of patients with dabrafenib plus trametinib treatment per treatment intent		Up to approximately 2.2 years
Number and percentage of patients with dabrafenib plus trametinib treatment per treatment setting		Up to approximately 2.2 years
Number and percentage of patients per type of D+T treatment change		Up to approximately 2.2 years
Number and percentage of patients per reason for D+T treatment change		Up to approximately 2.2 years
Mean duration of D+T, if not ongoing to end of study follow-up		Up to approximately 2.2 years
rwORR of dabrafenib plus trametinib among non-mucosal melanoma patients (FAS)		Up to approximately 2.6 years
Real-world disease control rate (rwDCR) of D+T (FAS)	rwDCR was defined as the percentage of patients with a best overall response of complete response (CR) or partial response (PR) or stable disease (SD) or non-CR or non-progressive disease (non-PD), per RECIST version 1.1 or as documented per physician assessment, as available.	Up to approximately 2.6 years
Real-world duration of response (rwDOR) of dabrafenib plus trametinib	For the subset of patients with CR or PR, rwDORn was defined as the time from the date of the first documented CR or PR per RECIST version 1.1 or as documented per physician assessment as available, to the first disease progression or death due to any cause.	Up to approximately 2.6 years
Real-world progression-free survival (rwPFS) for dabrafenib plus trametinib (FAS)	rwPFS was defined as the time from the start of treatment to the first documented disease progression or death due to any cause.	Up to approximately 2.6 years
Real-world overall survival (rwOS) since D+T initiation (FAS)	rwOS was defined as the time from start of treatment to death due to any cause.	Up to approximately 2.6 years
Time to treatment discontinuation (FAS)		Up to approximately 2.6 years
Number and percentage of patients with adverse events of special interest (AESIs) (FAS)	AESIs were defined based on the case retrieval strategy file available at the time of analysis.	Up to approximately 2.6 years
Number and percentage of patients with serious adverse events (SAEs) (FAS)		Up to approximately 2.6 years
rwPFS for dabrafenib plus trametinib (MMS), by immunotherapy use	rwPFS was defined as the time from the start of treatment to the first documented disease progression or death due to any cause.	Up to approximately 2.6 years
rwPFS for dabrafenib plus trametinib (NMS), by immunotherapy use	rwPFS was defined as the time from the start of treatment to the first documented disease progression or death due to any cause.	Up to approximately 2.6 years
rwOS since D+T initiation (MMS), by immunotherapy use	rwOS was defined as the time from start of treatment to death due to any cause.	Up to approximately 2.6 years
rwOS since D+T initiation (NMS), by immunotherapy use	rwOS was defined as the time from start of treatment to death due to any cause.	Up to approximately 2.6 years
Number and percentage of patients with systemic anti-neoplastic treatment after D+T		Up to approximately 2.6 years
Number and percentage of patients with systemic anti-neoplastic treatment after D+T per line of treatment		Up to approximately 2.6 years
Number and percentage of patients with systemic anti-neoplastic treatment after D+T and treatment ongoing at end of follow up		Up to approximately 2.6 years
Number and percentage of patients with systemic anti-neoplastic treatment after D+T per treatment type		Up to approximately 2.6 years
Number and percentage of patients per reason for immunotherapy discontinuation		Up to approximately 2.6 years
Number and percentage of patients with systemic anti-neoplastic treatment after D+T with best overall tumor response		Up to approximately 2.6 years
Number and percentage of patients who had systemic anti-neoplastic treatment after D+T treatment		Up to approximately 2.6 years
Number and percentage of patients who had systemic anti-neoplastic treatment after D+T treatment per medication		Up to approximately 2.6 years
Number and percentage of patients per concomitant medication		Up to approximately 2.2 years
Real-world overall survival since the first anti-neoplastic drug treatment for advanced/metastatic melanoma (FAS)		Up to approximately 2.6 years
Real-world overall survival since the first anti-neoplastic drug for advanced/metastatic melanoma (NMS), by immunotherapy use		Up to approximately 2.6 years

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2022
• Primary Completion (Actual): June 29, 2023
• Study Completion (Actual): June 29, 2023

Study Registration Dates

• First Submitted: March 22, 2024
• First Submitted That Met QC Criteria: March 22, 2024
• First Posted (Actual): March 29, 2024

Study Record Updates

• Last Update Posted (Actual): March 29, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Melanoma
• Other Study ID Numbers: CDRB436B2407