Tafinlar (dabrafenib) in combination with Mekinist (trametinib) results in superior progression-free survival for patients with BRAF-mutated advanced melanoma

What's exciting about Tafinlar?

A recent phase III study demonstrated a significant improvement in progression-free survival for Tafinlar plus Mekinist compared to Tafinlar plus placebo when given as first-line therapy in patients with BRAFV600E/K-mutated unresectable or metastatic melanoma (Long GV, et al. 2014). However, improvement in overall survival has not been demonstrated. Results from a phase I/II clinical study indicate that the combination is also efficacious in patients previously treated with one of several BRAF inhibitors (Flaherty, et.al. 2011). Combination therapy may be associated with less cutaneous toxicity than monotherapy.

What are Tafinlar's side effects?

Tafinlar in combination with Mekinist can cause serious side effects, some of which can be life threatening including: new primary cutaneous melanomas (though combination therapy reduced the incidence of cutaneous squamous-cell carcinoma development from 19% in the monotherapy group to 7% in the combination group (Flaherty, et.al. 2012), tumor promotion in wild type BRAF melanoma, hemorrhagic events, venous thromboembolic events, cardiomyopathy, ocular toxicities, interstitial lung disease (ILD), serious febrile drug reactions, serious skin toxicity, hyperglycemia, hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, and embryofetal toxicity. The most frequently occurring adverse reactions from the combination were pyrexia, chills, fatigue, rash, nausea, vomiting, diarrhea, abdominal pain, peripheral edema, cough, headache, athralgia, night sweats, decreased appetite, constipation, and myalgia. Regular dermatologic evaluation with referral to a dermatologist is recommended. Patients should also be educated to report the development of other adverse reactions such as joint pain and swelling. See the FDA drug label.

How can my patient get access to Tafinlar?

Tafinlar is approved for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test. Read about approved tests for detection of BRAF V600 mutations in melanoma. Tafinlar monotherapy or Tafinlar in combination with Mekinist are preferred regimens for patients whose tumors harbor the BRAF V600E or V600K aberration (see the NCCN guidelines).

 References

Summary

Name(s) Target Manufacturer Status
Tafinlar, dabrafenib BRAF V600D, BRAF V600K, BRAF, RAF1, BRAF V600E GlaxoSmithKline FDA approved for: Melanoma, BRAF V600E Mutated

Clinical Trials

Trial Drug Status Phase
A Study of the BRAF Inhibitor Dabrafenib in Combination With the MEK Inhibitor Trametinib in the Adjuvant Treatment of High-risk BRAF V600 Mutation-positive Melanoma After Surgical Resection. [NCT01682083] Mekinist, Tafinlar Recruiting Phase 3
Dabrafenib and Trametinib Followed by Ipilimumab and Nivolumab or Ipilimumab and Nivolumab Followed by Dabrafenib and Trametinib in Treating Patients With Stage III-IV BRAFV600 Melanoma [NCT02224781] Mekinist, Tafinlar, Yervoy, nivolumab Not yet recruiting Phase 3
Combi-Neo Study for Stage IV Melanoma [NCT02231775] Mekinist, Tafinlar Not yet recruiting Phase 2
Dabrafenib and Trametinib in Treating Patients With Stage III-IV BRAF Mutant Melanoma That Cannot Be Removed by Surgery [NCT02199730] Mekinist, Tafinlar Recruiting Phase 2
Dabrafenib and Trametinib in Treating Patients With Stage III-IV BRAF Mutant Melanoma That Cannot Be Removed by Surgery [NCT02196181] Mekinist, Tafinlar Recruiting Phase 2
Dabrafenib/Trametinib, BRAF or BRAF AND MEK Pre-op With BRAF and MEK Post-op, Phase IIB, Melanoma With Brain Mets,Biomarkers and Metabolites [NCT01978236] Mekinist, Tafinlar Recruiting Phase 2
Dabrafenib Alone and in Combination With Trametinib Before Surgery in Treating Patients With Locally or Regionally Advanced Melanoma That Can Be Removed By Surgery [NCT01701037] Mekinist, Tafinlar Recruiting Phase 2
A Phase 2 Prospective Trial of Dabrafenib With Stereotactic Radiosurgery in BRAFV600E Melanoma Brain Metastases [NCT01721603] Tafinlar Recruiting Phase 2
Adjuvant Dabrafenib (GSK2118436) in Patients With Surgically Resected AJCC Stage IIIC Melanoma Characterized by a BRAFV600E/K Mutation [NCT01682213] Tafinlar Recruiting Phase 2
LCCC 1128: Open Label Phase II Trial of the BRAF Inhibitor (Dabrafenib) and the MEK Inhibitor (Trametinib) in Unresectable Stage III and Stage IV BRAF Mutant Melanoma; Correlation of Resistance With the Kinome and Functional Mutations [NCT01726738] Mekinist, Tafinlar Recruiting Phase 2
An Open-Label Phase II Study of the Combination of GSK2118436 and GSK1120212 in Patients With Metastatic Melanoma Which is Refractory or Resistant to BRAF Inhibitor [NCT01619774] Mekinist, Tafinlar Recruiting Phase 2
Study to Evaluate Treatment of Dabrafenib Plus Trametinib in Subjects With BRAF Mutation-Positive Melanoma That Has Metastasized to the Brain [NCT02039947] Mekinist, Tafinlar Recruiting Phase 2
Study of Dabrafenib, Trametinib and Metformin for Melanoma Patients [NCT02143050] Mekinist, Metformin, Tafinlar Recruiting Phase 1/Phase 2
A Study of the Safety and Efficacy of Pembrolizumab (MK-3475) in Combination With Trametinib and Dabrafenib in Participants With Advanced Melanoma (MK-3475-022) [NCT02130466] Keytruda, Mekinist, Tafinlar Recruiting Phase 1/Phase 2
Dabrafenib, Trametinib, and Navitoclax in Treating Patients With Solid Tumors That Are Metastatic or Cannot be Removed by Surgery [NCT01970956] ABT-263, Mekinist, Tafinlar Recruiting Phase 1/Phase 2
Dabrafenib, Trametinib, and Navitoclax in Treating Patients With Solid Tumors That Are Metastatic or Cannot be Removed by Surgery [NCT01989585] ABT-263, Mekinist, Tafinlar Recruiting Phase 1/Phase 2
Phase 1 Safety and Tolerability of MEDI4736 in Combination With Dabrafenib and Trametinib or With Trametinib Alone [NCT02027961] MEDI4736, Mekinist, Tafinlar Recruiting Phase 1/Phase 2
Ipilimumab and Dabrafenib in the 1st Line Tx of Unresectable Stage III/IV Melanoma [NCT02200562] Tafinlar, Yervoy Not yet recruiting Phase 1/Phase 2
A Phase 1b/2a Study Evaluating AMG 232 in Metastatic Melanoma [NCT02110355] AMG 232, Mekinist, Tafinlar Not yet recruiting Phase 1/Phase 2
Dabrafenib in Treating Patients With Solid Tumors and Kidney or Liver Dysfunction [NCT01907802] Tafinlar Recruiting Phase 1
Dabrafenib and Pazopanib Hydrochloride in Treating Patients With Advanced Malignant Tumors [NCT01713972] Tafinlar, Votrient Recruiting Phase 1
A Study to Evaluate the Effect of Repeat Oral Dosing of GSK2118436 on Cardiac Repolarization in Subjects With V600 BRAF Mutation-Positive Tumors [NCT01738451] Tafinlar Recruiting Phase 1
Ipilimumab With or Without Dabrafenib, and/or Trametinib in Treating Patients With Melanoma That is Metastatic or Cannot Be Removed by Surgery [NCT01940809] Mekinist, Tafinlar, Yervoy Recruiting Phase 1
A Rollover Study to Provide Continued Treatment With GSK2118436 to Subjects With BRAF Mutation-Positive Tumors [NCT01231594] Mekinist, Tafinlar Recruiting Phase 1
Hsp90 Inhibitor AT13387, Dabrafenib, and Trametinib in Treating Patients With Recurrent Melanoma That is Metastatic or Cannot be Removed by Surgery [NCT02097225] AT13387, Mekinist, Tafinlar Recruiting Phase 1
Effects of Dabrafenib on the Single Dose Pharmacokinetics (PK) of Rosuvastatin and Midazolam [NCT02082665] Crestor, Midazolam, Tafinlar Not yet recruiting Phase 1
A Pharmacokinetics (PK) Study of the Effects Rabeprazole and Rifampin on Dabrafenib in Subjects With BRAF V600 Mutation Positive Tumors [NCT01954043] AcipHex, Tafinlar, rifampin Recruiting Phase 1
Study of Dabrafenib +/- Trametinib in Combination With Ipilimumab for V600E/K Mutation Positive Metastatic or Unresectable Melanoma [NCT01767454] Mekinist, Tafinlar, Yervoy Recruiting Phase 1
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