1. Medicines
  2. Oncology
  3. TAFINLAR® (dabrafenib) + MEKINIST® (trametinib) in Melanoma
  4. Safety profile
  5. Pooled COMBI-v and COMBI-d Safety

Prescribing information

 

Pooled COMBI-v and COMBI-d Safety

       

Well-established safety profile1–3

Key Safety Profile Insights From COMBI-v and COMBI-d Trials in Metastatic Melanoma

TAFINLAR (dabrafenib) + MEKINIST (trametinib) combination has a well-established safety profile.

 

 

No new safety signals were seen at five years in the pooled analysis of COMBI-v and COMBI-d.1

The most common adverse events observed with TAFINLAR + MEKINIST in the pooled five-year analysis included: pyrexia, nausea, diarrhoea, fatigue, headache, chills, and vomiting.1

 

Please visit the COMBI-v efficacy, COMBI-d efficacy and pooled efficacy pages for further information on the two trials and the landmark five-year pooled analysis.

TAFINLAR + MEKINIST has a well-established adverse event profile, and no new safety signals were seen at five years1–3

 

  • In the pooled analysis, adverse events led to permanent discontinuation of TAFINLAR + MEKINIST in <20% of patients.1
  • No treatment-related deaths were reported in the five-year pooled analysis.1

 

All-causality adverse events occurring in ≥20% of patients treated with TAFINLAR + MEKINIST(five-year pooled analysis)1

 

Image of table showing All-causality adverse events occurring in ≥20% of patients treated with TAFINLAR + MEKINIST(five-year pooled analysis)

Incidence of adverse events decreased over a three year period in patients who received TAFINLAR + MEKINIST4

 

  • In a separate pooled analysis of the three-year data from the COMBI-v and COMBI-d trials, the incidence of adverse events decreased over time in patients completing at least 36 months of treatment (n=50).4
  • The incidence of pyrexia more than halved from 60% at 0–6 months to 12% at 30–36 months of treatment.4

 

Incidence of adverse events (≥15%) over time in patients treated with TAFINLAR + MEKINIST for ≥36 months (pooled analysis at three years)4

 

Image of graph showing Incidence of adverse events (≥15%) over time in patients treated with TAFINLAR + MEKINIST for ≥36 months (pooled analysis at three years)4

 

Analysis of Pyrexia in Patients Treated with TAFINLAR + MEKINIST Across Clinical Trials*

  • Across TAFINLAR + MEKINIST clinical trials (n=1076)*, 39% of patients treated with TAFINLAR + MEKINIST did not experience a pyrexia event, while 32% of patients experienced only one or two events.5
  • The majority of pyrexia events were mild or moderate (Grade 1/2). Only 9% of patients treated with TAFINLAR + MEKINIST experienced Grade 3 events and 0.2% of patients experienced Grade 4 events.5
  • Most pyrexia events were completely resolved with either temporary dose interruption or no dose change.5
  • Only 6% of patients discontinued treatment with TAFINLAR or MEKINIST due to pyrexia.5

 

Single vs. multiple occurrences of pyrexia in all patients enrolled in clinical trials (n=1076)*

The data are based on a pooled analysis of pyrexia occurrence across four clinical trials* representing the largest analysis of a BRAF inhibitor + MEK inhibitor-induced pyrexia to date.4

 

Image of graph showing Single vs. multiple occurrences of pyrexia in all patients enrolled in clinical trials (n=1076)*

*Pyrexia was analysed from the following clinical trials in melanoma and in metastatic non-small cell lung cancer (NSCLC): Registrational Phase II trial (NCT01336634) in metastatic non-small cell lung cancer (n=82); COMBI-AD in resected Stage III melanoma (n=435); COMBI-d in unresectable or metastatic melanoma (n=209); COMBI-v in unresectable or metastatic melanoma (n=350).

 

Please consult the TAFINLAR + MEKINIST SPCs for a full list of adverse events.

SPC for TAFINLAR GB
SPC for TAFINLAR NI
SPC for MEKINIST GB
SPC for MEKINIST NI

 

Please visit the management of patients with BRAF V600-positive melanoma page for further information on monitoring for, and managing, pyrexia in patients receiving TAFINLAR + MEKINIST.

 

References

  1. Robert C, et al. N Engl J Med 2019;381:626–636.
  2. TAFINLAR (dabrafenib) Summary of Product Characteristics.
  3. MEKINIST (trametinib) Summary of Product Characteristics.
  4. Grob JJ, et al. Presented at SMR 2016; 6–9 November, Boston, MA, USA.
  5. Robert C, et al. Presented at ESMO 2019; 27 September – 1 October, Barcelona, Spain.
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UK | August 2022 | 100917-1

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 via [email protected] or online through the pharmacovigilance intake (PVI) tool at www.novartis.com/report
If you have a question about the product, please contact Medical Information on 01276 698370 or by email at [email protected]