Prescribing information

 

   

Well-established safety profile1–3

Key Safety Profile Insights

TAFINLAR (dabrafenib) + MEKINIST (trametinib) in the adjuvant setting has a well-established safety profile.1 

 

The most common adverse events observed with TAFINLAR + MEKINIST in the COMBI-AD study included: pyrexia, fatigue and nausea.6

No safety analysis was performed at the five-year follow-up of COMBI-AD, as no new safety data were generated since the primary analysis when the last patient was treated on 1 December 2015.1,6

 

Adverse events in the adjuvant setting (COMBI-AD trial) were generally consistent with those seen in the metastatic setting (COMBI-v and COMBI-d trials)4,5

 

  • All scheduled doses were completed by 63% of patients (272 of 435) on TAFINLAR, by 64% of patients (277 of 435) on MEKINIST, and by 53% of patients (227 of 432) on placebo.6
  • The majority of patients completed the scheduled 12 months of combination TAFINLAR + MEKINIST with a median dose that was close to the scheduled dose for each drug. Less than one third (26%) of the patients treated with TAFINLAR + MEKINIST discontinued treatment because of an adverse event (AE).6
  • The peak onset of all AEs occurring in ≥15% of patients in the TAFINLAR + MEKINIST arm occurred within the first three months of treatment.7
  • Frequencies of dose reductions or dose interruptions decreased as duration of treatment increased.7

Adverse events in the COMBI-AD study6,8

 

Image of table detailing adverse events in the COMBI-AD study6,8

Most common adverse events (>20% of patients) in the COMBI-AD study6,8

 

Image of table detailing the most common adverse events (>20% of patients) in the COMBI-AD study6,8

In the adjuvant treatment of patients with Stage III melanoma, the most common AE associated with TAFINLAR + MEKINIST treatment was pyrexia:

  • The majority of pyrexia events were Grade 1 or 2.6
  • Patients with serious non-infectious febrile events responded well to dose interruption and/or dose reduction and supportive care.2

Adverse events generally first occurred during the first three months of adjuvant treatment with TAFINLAR + MEKINIST. The peak onset of all adverse events occurring in ≥15% of patients treated with adjuvant TAFINLAR + MEKINIST occurred within the first three months of treatment.7

First occurence of adverse events in the COMBI-AD study*7

 

Image of graph detailing first occurence of adverse events in the COMBI-AD study*7

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

  • Across four 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.4
  • 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.4
  • Most pyrexia events were completely resolved with either temporary dose interruption or no dose change.4
  • Only 6% of patients discontinued treatment with TAFINLAR or MEKINIST due to pyrexia.4

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

These 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 detailing 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
SPC for MEKINIST

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

 

References

  1. Dummer R, et al. N Engl J Med 2020; DOI: 10.1056/NEJMoa2005493.
  2. TAFINLAR (dabrafenib) Summary of Product Characteristics.
  3. MEKINIST (trametinib) Summary of Product Characteristics.
  4. Robert C, et al. Presented at ESMO 2019;27 September – 1 October, Barcelona, Spain
  5. Robert C, et al. N Engl Med 2019;381:626–636.
  6. Long GV, et al. N Engl J Med 2017;377:1813–1823.
  7. Atkinson V, et al. Presented at ESMO 2018;19–23 October, Munich, Germany.
  8. Hauschild A, et al. Presented at ESMO 2017;8–12 September, Madrid, Spain.
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UK | December 2020 | 100878
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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.report.novartis.com
If you have a question about the product, please contact Medical Information on 01276 698370 or by email at [email protected]