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
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
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
*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 SmPCs for a full list of adverse events.
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.
- Dummer R, et al. N Engl J Med 2020; DOI: 10.1056/NEJMoa2005493.
- TAFINLAR (dabrafenib) Summary of Product Characteristics.
- MEKINIST (trametinib) Summary of Product Characteristics.
- Robert C, et al. Presented at ESMO 2019;27 September – 1 October, Barcelona, Spain
- Robert C, et al. N Engl Med 2019;381:626–636.
- Long GV, et al. N Engl J Med 2017;377:1813–1823.
- Atkinson V, et al. Presented at ESMO 2018;19–23 October, Munich, Germany.
- Hauschild A, et al. Presented at ESMO 2017;8–12 September, Madrid, Spain.