New Triple Combination Therapy for Skin Cancer

Published September 24th, 2020 by Dr. Sara Fisher, PharmD
Fact Checked by
Chris Riley

We all hear the warnings about skin cancer. Protect yourself from ultraviolet (UV) rays - wear sunscreen, stay in the shade, avoid tanning beds. But what is the big deal? Skin cancer does not seem so scary when all you have to do is get a spot removed from your arm or face, right?

Wrong. Skin cancer can be extremely difficult to treat. Melanoma is the most serious type of skin cancer because it is most likely to spread in the body. Surgery to remove cancer spots can be effective, but medications are also used for treatment, especially if the cancer already spread.

Types of Skin Cancer

There are many types of skin cancer, but the three most common types are listed below. 

  1. Basal cell carcinoma is the most common type of skin cancer and looks like a small growth, bump or off-colored patch of skin. This type is normally found on the head, neck and arms. If this is not caught before it grows, it may damage bones and nerves.
  2. Squamous cell carcinoma is the second most common and usually looks like a red bump, scaly patch or an open sore. This type is normally found in areas of high sun exposure, like the head and face, neck, arms, and back. Catching this type before it grows will prevent damaged skin.
  3. Melanoma is the third most common and usually develops within a mole or appears as a dark spot on the skin. Melanoma is generally considered the most serious skin cancer because it is more likely to spread, causing more deaths than the other types. When melanoma spreads through the body, it is called advanced melanoma. 

New Advanced Melanoma Treatment

Melanoma is usually treated with surgery to remove the skin cancer. Treating advanced melanoma requires medication in addition to surgery. Instead of just one medication, the most effective way to treat advanced melanoma is by using a combination of medications. 

The U.S. Food and Drug Administration (FDA) approved the first triple combination therapy for advanced melanoma in July of 2020 – atezolizumab (Tecentriq), cobimetinib (Cotellic) and vemurafenib (Zelboraf). 

Prior to this approval, advanced melanoma was typically treated with a single medication or a combination of two medications. Cobimetinib and vemurafenib can be used together as a two-drug combination, which was previously FDA-approved for advanced melanoma. 

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How It Works

The three medications work in three different ways. Atezolizumab is immunotherapy, or an immune checkpoint inhibitor, given through the veins (IV) once every 2 weeks. It is used for many other types of cancer, but this is its first approval for melanoma. 

Cobimetinib and Vemurafenib are both considered targeted therapy. The melanoma must have a specific target called BRAF V600 in order for these medications to work. About half of patients with melanoma have this target. Cobimetinib is an oral medication given daily for three weeks, then a one-week break. Vemurafenib is an oral medication given twice daily, every day with no break. 

The clinical trial evaluating the three medications showed that adding  atezolizumab to  cobimetinib and vemurafenib increased the amount of time when the cancer is not getting worse by about 4.5 months. The trial is still ongoing, so more results are expected in the future.

Notably, the National Comprehensive Cancer Network (NCCN) recommends using triple combination therapy of atezolizumab plus cobimetinib and vemurafenib as one of the first options for advanced melanoma based on the FDA-approval.  Note: The NCCN makes guidelines for treating all types of cancer. 

Treatment Side Effects

With the addition of atezolizumab to cobimetinib and vemurafenib, more side effects are expected. Based on the clinical trial, no new side effects were found by using the combination. The additional side effects expected are specific to atezolizumab. 

The most common side effects during triple combination therapy include the following:

  • Rash and itching
  • Feeling tired
  • Muscle pain
  • Nausea
  • Sensitivity to the sun
  • Diarrhea
  • Low thyroid levels


Skin cancer may sometimes seem easy to treat, but it can actually be very difficult. Once cancer  spreads in the body, there are less options for treatment. Reduce the risk of skin cancer by protecting yourself from harmful UV rays. If you already have skin cancer and you are interested in the new triple combination therapy, please ask your doctor to see if it is an option for you. 

Reference List

Centers for Disease Control and Prevention. Basic Information About Skin Cancer. Available from: Updated April 2020. Accessed 31 August 2020.

American Academy of Dermatology Association. Skin Cancer Resource Center. Available from: Updated 2020. Accessed 31 August 2020.

U.S. Food and Drug Administration (FDA). FDA Approves Atezolizumab for BRAF V600 Unresectable or Metastatic Melanoma. Available from: Updated 31 July 2020. Accessed 2 September 2020. 

American Cancer Society. Immune Checkpoint Inhibitors and Their Side Effects. Available from: Updated 27 December 2019. Accessed 2 September 2020. 

American Cancer Society. How Targeted Therapies Are Used to Treat Cancer. Available from: Updated 27 December 2019. Accessed 2 September 2020.

Pharmaceutical Technology GlobalData Healthcare. Triplet combinations emerging in the first-line treatment of melanoma. Available from: Updated 30 March 2020. Accessed 2 September 2020. 

Gutzmer R, Stroyakovskiy D, Gogas H, et al. Atezolizumab, vemurafenib, and cobimetinib as first-line treatment for unresectable advanced BRAFV600 mutation-positive melanoma (IMspire150): primary analysis of the randomised, double-blind, placebo-controlled, phase 3 trial [published correction appears in Lancet. 2020 Aug 15;396(10249):466]. Lancet. 2020;395(10240):1835-1844. Abstract available from:

National Comprehensive Cancer Network (NCCN). Cutaneous Melanoma (Version 4.2020). Available from: Published 1 September 2020. Accessed 2 September 2020.

Published September 24th, 2020 by Dr. Sara Fisher, PharmD
Fact Checked by
Chris Riley

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