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Pooled COMBI-v and COMBI-d efficacy

TAFINLAR® (dabrafenib) in combination with MEKINIST® (trametinib) is indicated in adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation.1,2

TAFINLAR in combination with MEKINIST is indicated for the adjuvant treatment of adult patients with Stage III melanoma with a BRAF V600 mutation, following complete resection.1,2

Common adverse events include:

  • TAFINLAR + MEKINIST: The most common adverse reactions (incidence ≥20%) for dabrafenib in combination with trametinib were pyrexia, fatigue, nausea, chills, headache, diarrhoea, vomiting, arthralgia and rash1,2

  • TAFINLAR: The most common adverse reactions (incidence >15%) reported with dabrafenib were hyperkeratosis, headache, pyrexia, arthralgia, fatigue, nausea, papilloma, alopecia, rash and vomiting1

  • MEKINIST: The most common adverse reactions (incidence ≥20%) for trametinib were rash, diarrhoea, fatigue, oedema peripheral, nausea and dermatitis acneiform2

For more safety information on TAFINLAR and MEKINIST, click here.

For the full safety profile, please refer to the Summary of Product Characteristics (SmPC) for TAFINLAR and MEKINIST.

Adverse event reporting: Details of how to report adverse events are available at the bottom of the page. Please refer to the respective SmPC for all licensed indications.

DURABLE five-year survival responses3

TAFINLAR + MEKINIST showed DURABLE responses up to five years in adult patients with BRAF V600-positive unresectable or metastatic melanoma3

Key clinical data insights from COMBI-v and COMBI-d

The efficacy and safety profile of TAFINLAR + MEKINIST for the treatment of adult patients with BRAF V600-positive unresectable or metastatic melanoma has been studied in two large Phase III trials: COMBI-v (vs vemurafenib) and COMBI-d (vs dabrafenib).4–6 A pooled analysis (N=563) was performed on the data from the TAFINLAR + MEKINIST treatment arms of these two trials. In a landmark five-year analysis of the trials, TAFINLAR + MEKINIST demonstrated that:

Pie chart icon showing a 34% audience in blue.

Approximately one in three (34%) patients treated with TAFINLAR + MEKINIST were alive at five years.3

Circle with the figure 55%.

More than half (55%) of patients with low tumour burden (normal LDH and <3 disease sites) treated with TAFINLAR + MEKINIST were alive at five years.3

Patients icon.

Nearly one in five (19%) patients treated with TAFINLAR + MEKINIST were still progression-free at five years.3

Icon of an ascending graph.

Complete response* was possible for nearly one in five (19%) patients treated with TAFINLAR + MEKINIST – for those patients with a complete response to treatment, overall survival (OS) was 71% and progression-free survival (PFS) was 49% at five years.3

Icon of a document and a magnifying glass.

Patients with favourable prognostic factors (normal LDH, <3 disease sites, ECOG performance status of 0) were more likely to achieve complete response and long-term OS than the overall population.3

OS at 5 years:

  • Normal LDH level: 43% vs 16% in patients above the upper limit of normal range

  • ECOG status 0: 88% vs 11% in patients with a score of 1 or higher

  • <3 disease sites: 73% vs 27% in patients with ≥3 disease sites

 

Complete response at 5 years:

  • Normal LDH level: 90% vs 10% above the upper limit of normal range

  • ECOG status 0: 86% vs 13% in patients with a score of 1 or higher

  • <3 disease sites: 84% vs 16% in patients with ≥3 disease sites

Please visit the Pooled COMBI-v and COMBI-d safety profile page for further information on the TAFINLAR + MEKINIST safety profile in the adjuvant setting.

COMBI-v and COMBI-d study design

The pooled population consisted of 563 first-line adult patients with BRAF V600-positive unresectable or metastatic melanoma. All patients in the analysis had been randomised to receive TAFINLAR 150 mg BID + MEKINIST 2 mg QD in either COMBI-v or COMBI-d. Median follow-up was 22 months (range, 0–76).3

Study design flow chart.
  

aCrossover was prohibited until the independent data and safety monitoring committee recommended stopping the study early due to superior efficacy in the combination arm. After the recommendation (July 2014), the study protocol was amended to allow patients in the vemurafenib group to cross over to the combination group.4
bCrossover was not allowed during the course of the study, in order to preserve the integrity of the OS endpoint. However, after the 2-year OS data cutoff, crossover was subsequently followed and may confound future OS analyses.5,6
cDefined as time from randomisation to death from any cause.4
dDefined as the time from randomisation until radiologic disease progression or death from any cause.5

*Indicates best overall response achieved at any point during the trials.

BID, twice daily; BRAF V600E/K, mutation of the BRAF gene at valine (V) 600 to either glutamate (E) or lysine (K); DOR, duration of response; ECOG, Eastern Cooperative Oncology Group; LDH, lactate dehydrogenase; MEK, mitogen-activated extracellular signal-regulated kinase; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; QD, once daily; R, randomised; SmPC, summary of product characteristics.

References

  1. TAFINLAR (dabrafenib). Summary of Product Characteristics.

  2. MEKINIST (trametinib). Summary of Product Characteristics.

  3. Robert C, et al. N Engl J Med 2019;381:626–636.

  4. Robert C, et al. N Engl J Med 2015;372:30–39.

  5. Long G, et al. N Engl J Med 2014;371:1877–1888.

  6. Long G, et al. Lancet 2015;386:444–451(inc. suppl).

  7. Robert C, et al. Pigment Cell Melanoma Res 2018;31:201.

UK | May 2025 | FA-11218759-2

Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Novartis online through the pharmacovigilance intake (PVI) tool at www.novartis.com/report, or alternatively email [email protected] or call 01276 698370.