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)

A well-characterized safety profile1,2

Tafinlar + Mekinist provides clinically meaningful responses and has a demonstrated safety profile in BRAF V600-mutated NSCLC1,2

  • The most common adverse reactions (≥20%) were: pyrexia, nausea, diarrhea, fatigue, chills, headache, vomiting, arthralgia, hypertension, rash, and cough1*

Adverse reactions occurring in ≥20% (all grades) of patients treated with Tafinlar + Mekinist (N=93).

aNeutropenia includes neutropenia and neutrophil count decreased. Neutrophil count decreased qualified as a neutropenia event.
bHemorrhage includes cases of hemoptysis, hematoma, epistaxis, purpura, hematuria, subarachnoid hemorrhage, gastric hemorrhage, urinary bladder hemorrhage, contusion, hematochezia, injection site hemorrhage, melaena, pulmonary and retroperitoneal hemorrhage.
cRash includes rash, rash generalized, rash papular, rash macular, rash maculopapular, and rash pustular.
dPruritus includes pruritus, pruritus generalized, and eye pruritus.
eHyperkeratosis includes hyperkeratosis, actinic keratosis, seborrheic keratosis, and keratosis pilaris.
fAsthenia also includes fatigue and malaise.
gEdema includes generalized.
NR, not reported.

  • Pyrexia was one of the most common adverse reactions, reported by 55% of patients receiving Tafinlar + Mekinist for BRAF V600+ NSCLC3
  • 2 patients discontinued Tafinlar + Mekinist due to pyrexia3
  • 18% of patients discontinued Tafinlar + Mekinist due to adverse reactions3

*The safety of Tafinlar in combination with Mekinist has been evaluated in the integrated safety population of 641 patients with BRAF V600 mutant unresectable or metastatic melanoma and advanced NSCLC treated with Tafinlar 150 mg twice daily and Mekinist 2 mg once daily. Of these patients, 559 were treated with the combination for BRAF V600 mutant melanoma in two randomized Phase III studies and 82 were treated with the combination for BRAF V600 mutant NSCLC in a multicohort, nonrandomized Phase II study.1

Warnings and precautions for Tafinlar (used as monotherapy or in combination with Mekinist):

  • Pyrexia including severe rigors, dehydration and hypotension (including acute renal insufficiency) reported. Incidence and severity increased when used in combination with Mekinist. Monitoring serum creatinine and renal function. Serious non-infectious febrile events observed. For management of Pyrexia, dose modification guidelines should be followed.
  • Cutaneous Squamous Cell Carcinoma (cuSCC) and new primary melanoma: Skin examination prior, during, and for 6 months after discontinuation of treatment or until initiation of another anti-neoplastic therapy.
  • Non-cutaneous secondary / recurrent malignancy: Monitoring as clinically appropriate for up to 6 months after discontinuation of Tafinlar or until initiation of another anti-neoplastic therapy.
  • Pancreatitis: Unexplained abdominal pain should be promptly investigated to include measurement of serum amylase and lipase. Close monitoring when re-starting Tafinlar.
  • Uveitis: Monitoring patients for visual signs and symptoms during therapy.

Tafinlar in combination with Mekinist:

  • Hemorrhage: Hemorrhagic events, including major and fatal hemorrhagic events have occurred in patients taking Tafinlar in combination with Mekinist.

Warnings and precautions for Mekinist (used as monotherapy or in combination with Tafinlar):

  • Left ventricular ejection fraction (LVEF) reduction / Left ventricular dysfunction: Cases of LVEF decrease reported. Should be used with caution when conditions could impair left ventricular function. All patients should be evaluated for LVEF prior to initiation of treatment with continued evaluation during treatment. Consider dose modification guidelines.
  • Hemorrhage: Hemorrhagic events, including major and fatal hemorrhagic events occurred in patients taking Mekinist as monotherapy and in combination with Tafinlar.
  • Visual impairment: Visual disturbances, including chorioretinopathy or retinal pigment epithelial detachment (RPED) and retinal vein occlusion (RVO) observed. Not recommended for patients with history of RVO. Ophthalmological evaluation should be performed at baseline and during treatment if clinically warranted. If retinal abnormally observed, treatment should be interrupted immediately and referral to specialist should be considered. Permanently discontinue treatment if RVO is noticed.
  • Rash: Observed in 60% of patients in monotherapy and 30% of patients in combination with Tafinlar.
  • Deep vein thrombosis (DVT)/pulmonary embolism (PE): Can occur when used as monotherapy or in combination with Tafinlar. Seek immediate medical care if patients develop symptoms of DVT or PE.
  • Pyrexia: Pyrexia including severe rigors, dehydration and hypotension (including acute renal insufficiency) reported. Incidence and severity increased when Mekinist used in combination with Tafinlar. During and following severe pyrexia events serum creatinine and other evidence of renal function should be monitored. Serious non-infectious febrile events have been observed. For management of pyrexia, dose modification guidelines should be followed.
  • Colitis and gastrointestinal perforation: Colitis and gastrointestinal perforation, including fatal outcome, have been reported. Treatment with Mekinist monotherapy or in combination with Tafinlar should be used with caution in patients with risk factors for gastrointestinal perforation, including a history of diverticulitis, metastases to the gastrointestinal tract and concomitant use of medications with a recognized risk of gastrointestinal perforation. If patients develop symptoms of colitis and gastrointestinal perforation they should immediately seek medical care.

References: 1. Tafinlar Summary of Product Characteristics. Novartis Pharmaceuticals Corp; 2017. 2. Planchard D, Besse B, Groen HJM, et al. Dabrafenib plus trametinib in patients with previously treated BRAFV600E-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. Lancet Oncol. 2016;17(7):984-993. 3. Tafinlar [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2017.