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ASCO 2016
13
DECEMBER 2016
First Line. First Fight.
Set
goals.
Target
control.
Expect
results.
TARGET
first line disease control
7out of 10
patients achieved a complete or
partial response
3–5
9 out of 10
patients experienced clinical benefit
with
TAFINLAR
®
+ MEKINIST
®
vs BRAFi
monotherapy
3–5
FIRST LINE TAFINLAR
®
+ MEKINIST
®
… confidence in FIGHTING
BRAFV600+ stage III (unresectable) and metastatic melanoma
1,2
SET
long-term goals for your
BRAFV600+ patients
TAFINLAR
®
+ MEKINIST
®
significantly improved OS vs
BRAFi monotherapy across 3 pivotal,
head-to-head trials
3–7
Overall survival:
44% of patients
alive at
3-years
with
58%
of these patients
still receiving
TAFINLAR
®
+ MEKINIST
®
treatment
7
Indication:
trametinib in combination with dabrafenib is indicated for the treatment of patients with BRAF V600 mutation positive unresectable Stage III or metastatic (Stage IV) melanoma. Confirmation
of BRAF V600 mutation with approved/validated test required.
Contraindications:
trametinib in combination with dabrafenib — hypersensitivity to the actives, or excipients. See full PI^.
Precautions:
trametinib in combination with dabrafenib — non-cutaneous malignancies, haemorrhage, cardiomyopathy, ocular adverse events, retinal pigment epithelial detachment, retinal vein occlusion, uveitis, iritis,
interstitial lung disease, pneumonitis, pyrexia, serious non-infectious febrile events, serious skin toxicity, cutaneous squamous cell carcinoma, new primary melanoma, non-cutaneous malignancy, renal
failure, hepatic events, pancreatitis, hyperglycaemia, effects on fertility, pregnancy (category D), lactation, paediatric use, and use in elderly. See full PI^.
Interactions:
trametinib is unlikely to interact with
CYP isoenzymes or transporters. Small decrease (16 %) in trametinib bioavailability with dabrafenib co-administration; dabrafenib — strong inhibitors or inducers of CYP2C8 or CYP3A4, proton pump
inhibitors, medicinal products affected by induction of CYP3A4, CYP2C9, CYP2B6, CYP2C8, CYP2C19, UGT and transporters, hormonal contraceptives, warfarin, statins and OATP1B1 or OATP1B3
substrates. See full PI.
Adverse Events:
trametinib in combination with dabrafenib — very common: urinary tract infection (UTI), neutropenia, dizziness, haemorrhage, night sweats, muscle spasms, rash,
dry skin, dermatitis acneiform, actinic keratosis, erythema, pruritus, decreased appetite, dehydration, headache, cough, oropharyngeal pain, diarrhoea, nausea, vomiting, constipation, abdominal pain,
dry mouth, pyrexia, chills, fatigue, peripheral edema, arthralgia, myalgia, back pain, muscle spasm, pain in extremity, anaemia, insomnia, increased ALT/AST, increased alkaline phosphatase (ALP) and
hyperbilirubinemia. Common — thrombocytopenia, hyponatraemia, hypotension, gamma-glutamyltransferase (GGT) increase, hyperhidrosis, rhabdomyolysis and QT prolongation. See full PI^.
Dosage
and Administration:
trametinib in combination with dabrafenib — dabrafenib 150 mg (as two 75 mg capsules) twice daily (total daily dose 300 mg), approximately 12 hours between doses, at least one
hour before or at least two hours after a meal, at similar times every day; trametinib 2 mg once daily, on an empty stomach, taken orally at the same time each day, with either the morning or evening dose
of dabrafenib. Dose adjust according to each PI. Trametinib dose adjustments below 1 mg not recommended. Dabrafenib dose adjustments below 50 mg twice daily not recommended; daily dose should
not exceed 150 mg twice daily. See full PI^. ^When trametinib is used in combination with dabrafenib, refer to the full individual PI documents.
(mektaf100715mv2)
References: 1.
Tafinlar (dabrafenib). Product Information.
2.
Mekinist (trametinib). Product Information.
3.
Long G et al.
Lancet
2015; 386(9992): 444–51.
4.
Robert C et al.
N Engl J Med
2015; 372: 30–9.
5.
Flaherty K et al.
N Engl J Med
2012; 367:1694–1703
6.
Long G et al.
J Clin Oncol
2016; 34(8): 871–8.
7.
Flaherty KT et al. Oral presentation at ASCO 2016: June 3–7, Chicago, Illinois.
Novartis Pharmaceuticals Australia Pty Ltd, ABN 18 004 244 160, 54 Waterloo Road, Macquarie Park, NSW 2113. Phone (02) 9805 3555. Item No.: MEL0190. Date of preparation:
September 2016. Tafinlar
®
and Mekinist
®
are registered trademarks of Novartis AG.
OS: Overall survival, BRAFi: BRAF inhibitor