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.

Unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test.

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.

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.

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]).

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.

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.

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 effects.

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.

...patients with resected BRAF V600–mutant stage III melanoma were randomly assigned to 12 months of adjuvant dabrafenib plus trametinib….3- and 4-year RFS rates were 59% (95% CI, 55% to 64%) and 54% (95% CI, 49% to 59%) in the dabrafenib plus trametinib arm and 40% (95% CI, 35% to 45%) and 38% (95% CI, 34% to 44%) in the placebo arm, respectively (HR, 0.49; 95% CI, 0.40 to 0.59). Distant metastasis–free survival also favored dabrafenib plus trametinib (HR, 0.53; 95% CI, 0.42 to 0.67)...

...Stage IIIc or Stage IV BRAF V600E/K cutaneous melanoma...

...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...

At 6 months, PR was achieved in 38%, stable disease in 52%, and progressive disease (PD) in 10%. Ten patients received a second treatment course: one complete response and 6 PRs were observed at 6 months….

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.

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.

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 vs PBO in subgroups of patients with microscopic or macroscopic lymph node involvement...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.

An observational, retrospective chart review was conducted in Italian patients with BRAF V600-mutant unresectable stage III/IV melanoma receiving dab + tram as part of the MAP….Overall response rate achieved in 243 of the 390 evaluable patients was 62.3% (95% CI 57.5-67.1). Median progression-free survival (PFS) was 9.3 months (95% CI 8.6-10.6)....Treatment of BRAF V600E-mutant metastatic melanoma with dab + tram in the real-world setting was effective and safe...

Patients (pts) with marginally resectable bulky stage III or resectable stage IV histologically confirmed melanoma were enrolled. BRAF V600 mutation status and pathology were confirmed...23 pts were treated with dabrafenib and trametinib, 3 pts were treated with vemurafenib and cobimetinib, and 3 with vemurafenib monotherapy.... BRAFi/MEKi combination is an effective and safe regimen in the perioperative treatment of melanoma.

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 .

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.

Dabrafenib plus trametinib results in a median OS of more than 2 years in BRAF inhibitor-naive patients with BRAF V600 mutation-positive metastatic melanoma, and approximately 20% were progression free at 3 years.

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.

A 72-year-old male patient was diagnosed with BRAF V600E-mutated melanoma...Ultimately, the patient was started on the combination therapy of dabrafenib and trametinib. This treatment resulted in a significant therapeutic response via normalization of bilirubin levels and an impressive radiological response of metastases just one month post-treatment initiation.

We herein report the case of a male patient with a BRAF V600E mutant metastatic melanoma, presenting with ileus caused by carcinomatous peritonitis, successfully treated with dabrafenib and trametinib via the nasogastric tube.

We report the case of a 61-year-old male patient with metastatic melanoma (B-Raf+). The tumor load of the patient was significantly reduced after the application of dabrafenib plus trametinib (“D+T”) and radiotherapy.

We describe here a case of a 68-year-old female presenting with melanoma harbouring a rare BRAF V600E 1799_1800 TG>AA mutation….we decided to repeat the BRAF mutation analysis using NGS testing with Actionable Tumor Panel UMI Kit (Qiagen, Milano, Italy) and a BRAF V600E 1799_1800 TG>AA mutation was detected. Consequently, the patient could start dabrafenib and trametinib combination treatment resulting in complete disease remission after 2 months of therapy (Fig. 2c). Currently, the patient has no signs of disease.