Relapse-Free Survival With Adjuvant Dabrafenib/Trametinib Therapy in Patients With BRAF V600-mutated Stage III/IV Melanoma

Relapse-Free Survival With Adjuvant Dabrafenib/Trametinib Therapy After Relapse on Adjuvant Checkpoint Inhibitor Therapy and Subsequent Surgical Resection in Patients With BRAF V600-mutated Stage III/IV Melanoma

This was a retrospective chart review study of all proto-oncogene B-Raf (BRAF) V600-mutated patients who received adjuvant checkpoint inhibitor (CPI) therapy, relapsed locoregionally or distantly, and were again resected to no evidence of disease (NED) and treated with adjuvant dabrafenib and trametinib (dab/tram) combination therapy.

Study Overview

• Status: Completed
• Conditions: BRAF V600 Mutated-Stage III/IV Melanoma

• Study Type: Observational
• Enrollment (Actual): 38

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • East Hanover, New Jersey, United States, 07936
      • Novartis Pharmaceuticals

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

This was a retrospective, noninterventional cohort study.

Description

Inclusion Criteria:

• Any patient at least 18 years of age at the time of diagnosis of stage III/IV melanoma.
• Received surgical resection with no residual disease following initial stage III/IV melanoma diagnosis.
• Documented local or central assay-positive for tumor BRAF V600E/K mutation.
• Received adjuvant CPI alone or in combination with any other immune treatment as their first adjuvant therapy.
• Following adjuvant CPI, relapsed (locoregionally or distantly) on or off treatment and was again rendered free of disease after subsequent surgical resection.
• Received additional adjuvant dab/tram combination therapy after failing adjuvant CPI and being subsequently resected to NED.

Exclusion Criteria:

• Previous administration of any BRAF- or mitogen-activated protein kinase (MEK)-targeted therapies.
• More than 120 days duration between surgery to render the patient NED after relapsing during or after adjuvant CPI therapy and initiation of dab/tram adjuvant therapy.
• Administration of any intervening antitumor medical and/or radiation therapy between failing adjuvant CPI and initiation of adjuvant dab/tram.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Dabrafenib and Trametinib Combination Therapy Cohort; Adult BRAF V600 patients with resected stage III/IV melanoma that relapsed during or after CPI as their first adjuvant therapy and were again rendered free of disease and received adjuvant dab/tram combination therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse-free Survival-2 (RFS-2)	RFS-2 was defined as the time from the study index date until the date of the earliest clinician-documented disease progression, death, or start of a new line of anticancer treatment due to disease progression. Patients without a progression event as described above were censored at the last available follow-up, defined as last known clinic visit or last known contact with the patient (if occurred outside the clinic setting). Index date was defined as the date that dab/tram combination therapy was initiated after being rendered disease-free for a second time following additional resection after prior relapse on initial CPI adjuvant therapy.	Up to 63 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS was defined as the time from the study index date until death due to any cause. Patients without a death event were censored at last available follow-up, defined as last known clinic visit or last known contact with the patient (if occurred outside the clinic setting). Index date was defined as the date that dab/tram combination therapy was initiated after being rendered disease-free for a second time following additional resection after prior relapse on initial CPI adjuvant therapy.	Up to 63 months
Distant Metastases-free Survival (DMFS)	DMFS was defined as the time from the study index date until the first observation of disease progression with distant metastasis. Patients without a DMFS event as described above were censored at last available follow-up, defined as last known clinic visit or last known contact with the patient (if occurred outside the clinic setting). Index date was defined as the date that dab/tram combination therapy was initiated after being rendered disease-free for a second time following additional resection after prior relapse on initial CPI adjuvant therapy.	Up to 63 months
Number of Patients with an Adverse Event (AE) Related to Dabrafenib and Trametinib Combination Therapy		Up to 63 months
Mean Number of Times an AE Related to Dabrafenib and Trametinib Combination Therapy was Experienced		Up to 63 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2022
• Primary Completion (Actual): November 16, 2023
• Study Completion (Actual): November 16, 2023

Study Registration Dates

• First Submitted: August 13, 2024
• First Submitted That Met QC Criteria: August 13, 2024
• First Posted (Actual): August 16, 2024

Study Record Updates

• Last Update Posted (Actual): August 16, 2024
• Last Update Submitted That Met QC Criteria: August 13, 2024
• Last Verified: August 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: CTMT212AUS65