Melanoma Treatment - Targeted Therapy

Targeted therapy is a form of treatment in which drugs (or other substances) are developed with the goal of destroying cancer cells while leaving normal cells intact. These drugs are designed to interfere with the specific molecules that are driving the growth and spread of the tumor. Because they are “targeted” to the tumor, these therapies may be more effective and associated with fewer side effects compared to chemotherapy and radiation therapy. A targeted therapy approach allows the classification of melanoma into different “subtypes” based on the genetic profile of the tumor. This facilitates personalized treatment as patients receive drugs based on the unique genetic profile, or subtype, of their tumor. Targeted therapies are usually taken in pills or capsules. 

Up-to-date recordings on a variety of melanoma treatments can be found on our Educational Recordings page.

FDA-Approved Targeted Therapies for Melanoma

Encorafenib (Braftovi™) + Binimetinib (Mektovi®)

FDA-approved in June 2018 for the treatment of unresectable or metastatic melanoma with a BRAF V600E or BRAF V600K mutation. The approval followed a phase 3 trial which showed the combination doubled median progression-free survival (mPFS) compared to vemurafenib as a single therapy. It is not indicated for the treatment of patients with wild-type BRAF melanoma. 

Vemurafenib (Zelboraf®) + Cobimetinib (Cotellic®)

FDA-approved in November 2015 for the treatment of BRAF V600 mutant melanoma. Vemurafenib was previously approved in 2011 but in research studies, this combination showed improved progression-free and overall survival compared to vemurafenib alone. 

Dabrafenib (Tafinlar®) + Trametinib (Mekinist®

FDA-approved in 2014 for demonstrating durable responses in patients with unresectable or metastatic melanomas that carry the BRAF V600E or V600K mutation. Randomized trials are in progress to assess the ability of the combination to improve time to progression and overall survival compared with dabrafenib alone. Most recently, in April 2018, Tafinlar and Mekinist were approved in combination for the adjuvant treatment of patients with melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test, and involvement of lymph node(s), following complete resection. Approval was based on an international, multi-center, randomized, double-blind, placebo-controlled trial in 870 patients with Stage III melanoma with BRAF V600E or V600K mutations. The major efficacy outcome was relapse-free survival (RFS). Patients who received the combination treatment had a statistically significant improvement in RFS compared with those receiving placebo.   

Dabrafenib (Tafinlar®)

FDA-approved in 2013 for the treatment of BRAF V600 mutant melanoma that cannot be removed by surgery. This drug is only approved for those patients who have tested positive for the BRAF mutation. It is not indicated for the treatment of patients with wild-type BRAF mutation.

Trametinib (Mekinist®)

FDA-approved in 2013 for the treatment of BRAF V600E or V600K mutations. It is a first-in-class MEK inhibitor approved for the treatment of unresectable or metastatic melanoma. It is not indicated for the treatment of patients who have received a prior BRAF inhibitor therapy.

Vemurafenib (Zelboraf®)

FDA-approved in 2011 for the treatment of BRAF V600E mutant melanoma that cannot be removed by surgery. This drug is only approved for those patients who have tested positive for the BRAF mutation. 

Additional Genomic and Biomarker Information

The MRF's webinar, Precision Medicine in Melanoma, may help you better understand the importance of genomic testing, biomarkers and what it means for the treatment of melanoma. 

Side Effects of Targeted Therapies

Side effects of targeted therapies are not the same as side effects of traditional cancer treatments, like chemotherapy. Side effects are not an indicator that the drug is working or not working. It is very important to report all side effects to your treatment team as soon as you notice them. Most side effects can be managed if they are treated early, and this may allow you to stay on the treatment longer. Because targeted therapies are still relatively new, little is known about the long-term side effects of these treatments. The most common side effects of targeted therapies include:

  • Fever
  • Rash
  • Itching
  • Sensitivity to sun
  • Development of squamous cell skin cancers
  • Joint pain