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Association details:
Evidence:
Evidence Level:
Sensitive: A1 - Approval
New
Source:
Excerpt:
TAFINLAR is indicated, in combination with trametinib, for...the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test.
Evidence Level:
Sensitive: A2 - Guideline
New
Source:
Excerpt:
Unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test.
Evidence Level:
Sensitive: B - Late Trials
Source:
Title:

Restricted mean survival time (RMST) and cure-rate modeling in estimating survival benefit with adjuvant dabrafenib (D) plus trametinib (T) treatment in melanoma Presentation Number

Published date:
09/14/2020
Excerpt:
RMST and cure rate were improved with D+T across AJCC 7 substages, with the greatest benefit observed in pts with high-risk baseline stage IIIB or IIIC. RMST and cure-rate models complement conventional statistical methods for 5-year COMBI-AD analysis, demonstrating significant clinical benefit with adjuvant D+T across all stage III substages in pts with melanoma.
Trial ID:
Evidence Level:
Sensitive: B - Late Trials
Title:

Five-Year Analysis of Adjuvant Dabrafenib plus Trametinib in Stage III Melanoma

Published date:
09/02/2020
Excerpt:
In the 5-year follow-up of a phase 3 trial involving patients who had resected stage III melanoma with BRAF V600E or V600K mutations, 12 months of adjuvant therapy with dabrafenib plus trametinib resulted in a longer duration of survival without relapse or distant metastasis than placebo with no apparent long-term toxic effects.
DOI:
10.1056/NEJMoa2005493
Trial ID:
Evidence Level:
Sensitive: B - Late Trials
Source:
Title:

Long-term benefit of adjuvant dabrafenib + trametinib (D+T) in patients (pts) with resected stage III BRAF V600–mutant melanoma: Five-year analysis of COMBI-AD.

Published date:
05/13/2020
Excerpt:
COMBI-AD is a randomized, Phase III trial evaluating 12 mo of adjuvant D 150 mg twice daily + T 2 mg once daily vs 2 matched PBOs in pts with resected stage III BRAF V600E/K–mutant melanoma...The 4- and 5-year RFS rates were 55% (95% CI, 50%-60%) and 52% (95% CI, 48%-58%) with D+T vs 38% (95% CI, 34%-43%) and 36% (95% CI, 32%-41%) with PBO. These findings match those estimated by the cure rate model. The RFS benefit with D+T was evident across all AJCC 7 substages (HR [95% CI]: IIIA, 0.61 [0.35-1.07]; IIIB, 0.50 [0.37-0.67]; IIIC, 0.48 [0.36-0.64]).
DOI:
10.1200/JCO.2020.38.15_suppl.10001
Trial ID:
Evidence Level:
Sensitive: B - Late Trials
Title:

Novartis' combination therapy Tafinlar + Mekinist granted FDA Priority Review for the adjuvant treatment of stage III BRAF V600 mutation-positive melanoma

Published date:
12/22/2017
Excerpt:
Novartis announced today the US Food and Drug Administration (FDA) has accepted the Company's supplemental New Drug Application (sNDA) for filing, and granted Priority Review designation for Tafinlar (dabrafenib) in combination with Mekinist (trametinib) for the adjuvant treatment of patients with stage III melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test, following complete resection.
Evidence Level:
Sensitive: B - Late Trials
Title:

Novartis combination adjuvant therapy Tafinlar + Mekinist receives FDA Breakthrough Therapy Designation for stage III BRAF V600 mutation-positive melanoma patients

Published date:
10/23/2017
Excerpt:
Novartis today announced that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) for Tafinlar (dabrafenib) in combination with Mekinist (trametinib) for the adjuvant treatment of patients with stage III melanoma with a BRAF V600 mutation following complete resection...The designation is based on results from COMBI-AD, a Phase III study of 870 patients with stage III BRAF V600E/K mutation-positive melanoma after complete surgical resection treated with Tafinlar + Mekinist.
Evidence Level:
Sensitive: B - Late Trials
New
Title:

Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametinib

Excerpt:
Dabrafenib plus trametinib, as compared with vemurafenib monotherapy, significantly improved overall survival in previously untreated patients with metastatic melanoma with BRAF V600E or V600K mutations, without increased overall toxicity.
DOI:
10.1056/NEJMoa1412690
Trial ID:
Evidence Level:
Sensitive: B - Late Trials
New
Title:

Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma

Excerpt:
Adjuvant use of combination therapy with dabrafenib plus trametinib resulted in a significantly lower risk of recurrence in patients with stage III melanoma with BRAF V600E or V600K mutations than the adjuvant use of placebo and was not associated with new toxic effect.
DOI:
10.1056/NEJMoa1708539
Evidence Level:
Sensitive: C2 – Inclusion Criteria
New
Go to data
Title:

Dabrafenib Plus Trametinib vs Vemurafenib Alone in Unresectable or Metastatic BRAF V600E/K Cutaneous Melanoma (COMBI-v)

Excerpt:
...Stage IIIc or Stage IV BRAF V600E/K cutaneous melanoma...
Trial ID:
Evidence Level:
Sensitive: C2 – Inclusion Criteria
New
Go to data
Title:

Dabrafenib With Trametinib in the Adjuvant Treatment of High-risk BRAF V600 Mutation-positive Melanoma (COMBI-AD). (COMBI-AD)

Excerpt:
...Completely resected histologically confirmed high-risk [Stage IIIa (LN metastasis more than 1 mm), IIIb or IIIc cutaneous melanoma determined to be V600E/K mutation positive by a central laboratory. Patients presenting with initial resectable lymph node recurrence after a diagnosis of Stage I or II melanoma are eligible...
Trial ID:
Less C2 evidence
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Expanded cohort and extended follow-up of neoadjuvant plus adjuvant (neo + adj) dabrafenib (D) and trametinib (T) in patients (pts) with surgically resectable stage (stg) III/IV melanoma.

Published date:
05/31/2023
Excerpt:
We conducted a single-center, phase II clinical trial (NCT02231775) evaluating neo + adj DT in pts with surgically resectable, RECIST measurable clinical stg III or oligometastatic stg IV BRAF V600E/K mutated melanoma....Neo + adj DT is feasible and safe in pts with surgically resectable BRAF mutated melanoma. With a median follow-up of 35 mos, median RFS, DMFS, and OS have not been reached for pts with a pCR after neo DT, and are all significantly prolonged compared to non-pCR pts.
DOI:
10.1200/JCO.2023.41.16_suppl.9583
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

Expanded cohort and extended follow-up of neoadjuvant plus adjuvant (neo + adj) dabrafenib (D) and trametinib (T) in patients (pts) with surgically resectable stage (stg) III/IV melanoma.

Published date:
05/25/2023
Excerpt:
We conducted a single-center, phase II clinical trial (NCT02231775) evaluating neo + adj DT in pts with surgically resectable, RECIST measurable clinical stg III or oligometastatic stg IV BRAF V600E/K mutated melanoma….These results demonstrate durable benefit for neo + adj DT in this high-risk pt population that achieve a pCR.
DOI:
10.1200/JCO.2023.41.16_suppl.9583
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

Adjuvant dabrafenib plus trametinib (D + T) versus placebo in patients with resected stage III BRAFV600-mutant melanoma: Updated 5-year distant metastases-free survival (DMFS) analysis of COMBI-AD.

Published date:
05/26/2022
Excerpt:
Patients with resected AJCC-7 stage III BRAFV600E/K-mutant melanoma were randomized to either D (150 mg twice daily) + T (2 mg once daily)...At 5 years, DMFS rates were higher for patients with AJCC-8 stages IIIB-D disease receiving adjuvant D + T vs PBO (table). Five-year DMFS rates also favored D + T...In this retrospective analysis, adjuvant D + T provided long-term DMFS benefit vs PBO in stage IIIB-D patients with resected BRAFV600E/K-mutant melanoma.
DOI:
10.1200/JCO.2022.40.16_suppl.9563
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

Clinical outcomes in patients with BRAFV600 mutant melanoma and undetectable circulating tumor DNA treated with dabrafenib and trametinib.

Published date:
05/13/2020
Excerpt:
Detection of ctDNA at baseline was associated with worse PFS (median BRAFV600 ctDNA positive = 5.8; 95% CI: 4.2-9.6 months, BRAFV600 ctDNA negative = 21.4 mos; 95% CI 10.4-NA; measured from registration to lead-in cycle 1, p = 0.001) and OS (BRAFV600 ctDNA positive = 17.8 mos; 95% CI 9.76-NA, BRAFV600 ctDNA negative = not reached; 95% CI NA-NA, p = 0.0021)....The absence of detectable BRAFV600 ctDNA at baseline is associated with improved PFS and OS in patients receiving treatment with dabrafenib and trametinib .
DOI:
10.1200/JCO.2020.38.15_suppl.10059
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Abstract CT013: SWOG S1320: Improved progression-free survival with continuous compared to intermittent dosing with dabrafenib and trametinib in patients with BRAF mutated melanoma

Published date:
04/27/2020
Excerpt:
S1320 is a randomized phase 2 clinical trial designed to determine whether intermittent versus continuous dosing of dabrafenib and trametinib improves progression-free survival (PFS) in patients with advanced BRAFV600E/K melanoma….Continuous dosing with the BRAF and MEK inhibitors dabrafenib and trametinib yields superior PFS compared with intermittent dosing.
DOI:
10.1158/1538-7445.AM2020-CT013
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
New
Title:

The extent of surgery for stage III melanoma: how much is appropriate?

Excerpt:
Furthermore, adjuvant-targeted therapy with dabrafenib and trametinib has improved survival outcomes in BRAFV600E and BRAFV600K-mutated melanomas. Three neoadjuvant trials have all shown high response rates, including complete responses, after short-term combination therapy with ipilimumab and nivolumab with no recurrences so far, although follow-up is still short.
DOI:
10.1016/S1470-2045(19)30099-3