For Healthcare Professionals Outside the US

For patients with BRAF V600 mutation–positive unresectable or metastatic melanoma

For patients with BRAF V600 mutation–positive advanced non-small cell lung cancer (NSCLC)

First-line Tafinlar + Mekinist sets a new benchmark with unprecedented survival at 3 years2,4

 

Tafinlar® (dabrafenib) + Mekinist® (trametinib) survival rate trials

COMBI-v: First-line Tafinlar + Mekinist sets a new benchmark with 45% long-term survival at 3 years2

Monotherapy overall survival probability Tafinlar® (dabrafenib) + Mekinist® (trametinib)

  • In COMBI-v, the median OS in patients treated with Tafinlar + Mekinist was 26.1 months vs 17.8 months with vemurafenib monotherapy2
  • In COMBI-v, of the patients in the Tafinlar + Mekinist arm still alive at 3 years, ≈ 5 of 10 (49%) were still on first-line Tafinlar + Mekinist2

COMBI-d: 44% of patients treated with first-line Tafinlar + Mekinist were alive at 3 years4

OS rate at 3 years with Tafinlar® (dabrafenib) + Mekinist® (trametinib)

  • In COMBI-d, the median OS in patients treated with Tafinlar + Mekinist was 25.1 months vs 18.7 months with Tafinlar monotherapy3
  • In COMBI-d, of the patients in the Tafinlar + Mekinist arm still alive at 3 years, ≈ 6 of 10 (58%) were still on first-line Tafinlar + Mekinist4

220 study: 28% OS rate at 5 years with Tafinlar + Mekinist6

 

220 study results

 

Survival benefit with Tafinlar + Mekinist maintained over time6

In the 220 study:

  • Among patients treated with Tafinlar + Mekinist with a best response of CR, the 5-year OS rate was 44% and median OS was 53.4 months6
  • 83% (45/54) of patients receiving Tafinlar monotherapy crossed over to Tafinlar + Mekinist, confounding results with Tafinlar monotherapy6

5-year OS rates were higher in patients with more favorable baseline prognostic factors treated with Tafinlar + Mekinist6

More than half of patients with normal LDH and <3 organ sites of metastasis were alive at 5 years with Tafinlar + Mekinist6

5 year overall survival.

These Phase II Tafinlar + Mekinist survival data further support that long-term benefit is achievable with targeted therapies6

 

100% (54/54) of patients in the Tafinlar + Mekinist arm achieved disease control6

17% of patients treated with Tafinlar + Mekinist achieved a complete response6

Disease control rate

 Among the 17% of patients in the Tafinlar + Mekinist arm with a complete response, 4 of 10 patients remained progression free at both 4 years and 5 years (median PFS=39.6 months)6

 

Post hoc pooled analysis: patient baseline factors associated with survival across the 3 randomized studies7

Treatment-naive patients who received Tafinlar + Mekinist across 3 randomized studies:

Study Randomized, na OS Events, n
220 Study 54 36
Phase 3 Trial COMBI-v 352 155
Phase 3 Trial COMBI-d 211 99
Total 617

290

  • Median duration of follow-up was 20.0 months
  • 221 patients (36%) remained progression free and alive at analysis

Patient baseline factors were analyzed to determine which factors influenced OS with first-line Tafinlar + Mekinist across the 3 randomized studies7

Baseline Factors That Were Evaluated Analyses That Were Conducted
  • Body mass index
  • Age
  • Sum of target lesion diameters
  • LDH categories
    • Normal (≤ ULN), elevated (> ULN)
    • Normal (≤ ULN), elevated (> 1 to ≤ 2 × ULN), highly elevated (> 2 × ULN)
  • Sex
  • ECOG performance status
  • Baseline visceral disease
  • Number of disease sites
  • Prior adjuvant immunotherapy
  • Univariate
  • Multivariate
  • Regression tree
  • Patients with normal LDH levels and < 3 disease sites were the largest patient population (38%) and had the best OS results (3-year survival rate of 70%)7
  • Patients with normal LDH levels had longer survival times than those who had elevated levels7

Regression tree analysis: identification of 5 distinct patient populations based on baseline LDH levels, number of disease sites, and ECOG performance status7

 

Regression tree analysis: identification of 5 distinct patient populations 

 

First-line Tafinlar + Mekinist from the 3 randomized studies showed optimal OS in patients with normal baseline LDH levels, < 3 disease sites, and ECOG performance status of 07

 

Tafinlar® (dabrafenib) + Mekinist® (trametinib) use after progression BRAF inhibitor monotherapy

 

From Long GV, et al. In: Proceedings from the Society for Melanoma Research; November 18–21, 2015; San Francisco, CA. Reprinted with author's permission.

The use of Tafinlar + Mekinist after progression on BRAF inhibitor monotherapy resulted in inferior survival compared with upfront usage8

Tafinlar® (dabrafenib) + Mekinist® (trametinib) overall survival

  • Before crossing over to Tafinlar + Mekinist after disease progression, patients initially randomized to Tafinlar monotherapy in the 220 study did derive clinical benefit from Tafinlar monotherapy (median progression-free survival with Tafinlar monotherapy was 5.8 months)9

 

ECOG, Eastern Cooperative Oncology Group; HR, hazard ratio; LDH, lactate dehydrogenase; OS, overall survival; ULN, upper limit of normal.



References: 1. Robert C, Karaszewska B, Schachter J, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015;372:30-39. 2. Robert C, Karaszewska B, Schachter J, et al. Three-year estimate of overall survival in COMBI-v, a randomized phase 3 study evaluating first-line dabrafenib + trametinib in patients with unresectable or metastatic BRAF V600E/K-mutant cutaneous melanoma. Presented at: European Society for Medical Oncology; October 7-11, 2016; Copenhagen, Denmark. 3. Long GV, Stroyakovskiy D, Gogas H, et al. Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial. Lancet. 2015;386(9992):444-451. 4. Flaherty KT, Davies MA, Grob J, et al. Genomic analysis and 3-year efficacy and safety update of COMBI-d. J Clin Oncol. 2016;34(suppl) [abstract 9502]. 5. Daud A, Weber J, Sosman J, et al. Updated overall survival for BRF113220: a phase 1-2 study of dabrafenib alone vs combined dabrafenib and trametinib in patients with BRAF V600 mutation-positive metastatic melanoma. J Clin Oncol. 2015:33(15 suppl) [abstract 9036]. 6. Long GV, Eroglu Z, Infante J, et al. Long-term outcomes in patients with BRAF V600-mutant metastatic melanoma who received dabrafenib combined with trametinib. J Clin Oncol. 2017:JCO2017741025. doi: 10.1200/JCO.2017.74.1025. 7. Long GV, Grob J-J, Davies MA, et al. Baseline and postbaseline characteristics associated with treatment benefit across dabrafenib and trametinib registration pooled data. Pigment Cell Melanoma Res. 2015;28(6):793. 8. Flaherty K, Daud A, Weber J, et al. Updated overall survival for BRF113220, a phase 1-2 study of dabrafenib alone vs combined dabrafenib and trametinib in patients with BRAF V600 mutation-positive metastatic melanoma. J Clin Oncol. 2014:32(5 suppl) [abstract 9010]. 9. Flaherty KT, Infante JR, Daud A, et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med. 2012;367(18):1694-1703.