Skin Cancer and Melanoma Facts: Symptoms and Treatment
Medically reviewed on Dec 7, 2017 by L. Anderson, PharmD.
What Is Skin Cancer?
There are 3 main types of skin cancer: basal cell carcinoma, squamous cell carcinoma (also called nonmelanoma skin cancer), and melanoma. Skin cancers begin in the top layer of the skin known as the epidermis. Most skin cancers are caused by excessive ultraviolet (UV) radiation, such as from the sun or tanning booths, but family history is important, too. It is important that skin cancers are found and treated early because they can invade and destroy nearby tissue and invade other organs.
- Basal cell carcinoma is a slow-growing cancer that starts in the upper layer of skin, but seldom spreads to other parts of the body.
- Squamous cell carcinoma also starts in the upper layer of skin and rarely spreads, but it does so more often than basal cell carcinoma.
- Melanoma is a malignancy of the melanocytes (pigment forming cells) and is the most serious form of skin cancer. Melanoma skin cancer can spread (metastasize) to other areas, such as the liver, lungs or brain. When the melanoma cancer cells spread, the disease is called metastatic melanoma rather than liver, lung or brain cancer.
What Makes Up the Skin?
The skin is the body's largest organ; the body's outer covering which protects it from heat, light, injury and infection. It regulates body temperature, and stores water, fat and vitamin D. The skin is made up of 3 layers:
- the epidermis
- the dermis
- the hypodermis
The epidermis contains the basal cells, squamous cells, and melanocytes (cells that produce a pigment called melanin which gives the skin its color), the cells most commonly affected by skin cancer. The dermis is an inner layer made of lymph vessels, hair follicles, sweat glands, and sebum, and the hypodermis is a deeper layer that contains fat and connective tissue.
Top 5 Skin Cancer Statistics
Skin cancer is the most common type of cancer in the United States.
- Annually over 5.4 million cases of nonmelanoma (basal cell or squamous cell) skin cancer occur.
- Approximately 80 percent of nonmelanoma skin cancers are basal cell carcinoma and 20 percent are squamous cell carcinoma. Basal cell is the most common skin cancer.
- According to current estimates, 40% to 50% of Americans who live to age 65 will have nonmelanoma skin cancer at least once.
- Melanoma is the most serious of the different skin cancers, and the number of people who develop melanoma is increasing at a faster rate than that of any other cancer.
- Add it up and there are more new cases of skin cancer than the total numbers of breast, prostate, lung and colon cancer combined.
What Are the Risk Factors for Skin Cancer?
A person's risk for skin cancer can be due to many factors. Ultraviolet (UV) radiation from the sun is the main cause of skin cancer. Artificial sources of UV radiation like sunlamps and tanning booths can also cause skin cancer. Any amount of UV radiation can be harmful, even if it does not lead to a burn. The risk of developing skin cancer or melanoma is also affected by where a person lives and by the lifetime exposure of UV radiation.
- Areas that get high levels of UV radiation from the sun increase your chances for skin cancer, such as higher elevations and areas closer to the equator, such as Texas or Florida in the US.
- Worldwide, the highest rates of skin cancer are found in areas that receive high amounts of UV radiation such as South Africa, Australia and New Zealand.
- Most skin cancers appear after age 50, but the sun's damaging effects begin at an early age. Therefore, protection should start in childhood to prevent skin cancer later in life.
- Family history of skin cancer, such as in a parent or sibling, and personal history of a previous skin cancer.
- Precancerous skin lesions known as actinic keratoses.
- Weakened immune system: for example, if you have cancer, AIDS or an organ transplant.
- A large numbers of moles or abnormal moles like dysplastic nevi.
- Exposure to UV radiation: UV radiation from the sun, sunlamps and tanning booths can cause skin damage and an increased risk of melanoma; radiation treatments for certain skin conditions like acne or eczema can also increase risk.
- Severe, blistering sunburns: having one or more severe, blistering sunburns as a child or teenager, or even as an adult are an increased risk for melanoma.
- Fair skin that freckles easily, and people with red or blond hair and blue or light-colored eyes.
Symptoms of Skin Cancer
Precancerous skin changes, known as actinic keratoses, occur due sun damage. Actinic keratoses can be found on the face, ears, arms or scalp.
Actinic keratoses typically appear as rough, scaly patches in a variety of colors such as brown, pink, or red. About 15% of actinic keratoses will change into squamous cell cancers of the skin; therefore, early treatment is important.
Basal and squamous cell skin cancers
Basal and squamous cell cancers are found mainly on areas of the skin that are exposed to the sun such as the head, face, neck, hands, and arms; however, skin cancer can occur anywhere. Skin cancers don't all look the same. The most common warning sign of skin cancer is a change on the skin, especially a new growth or a sore that doesn't heal, and may appears as:
- Pink or Red
- Peeling, scaly, or crusty
- Flat or thickened area
- Bleeding or cracked
Melanoma skin cancer
Melanoma is a serious type of skin cancer. You may notice a change in the size, shape, color, or feel of an existing mole. Other frequent findings are newly formed fine scales or itching in a mole. Melanomas can vary greatly in the ways they look, and may show one or many changes. They can occur anywhere: on the back, legs, arms, hands, feet and even in the skin lining the mouth, nose, and genitals.
Using the 5 letters "ABCDE" can help you remember what melanoma symptoms to watch for:
- Asymmetry: the shape of one half does not match the other.
- Border: the edges are often ragged, notched, blurred, or irregular in outline; the pigment may spread into the surrounding skin.
- Color: the color is uneven. Shades of black, brown, and tan may be present. Areas of white, gray, red, pink, or blue also may be seen.
- Diameter: there is a change in size, usually an increase. Melanomas are usually larger than the eraser of a pencil (5 mm or 1/4 inch).
- Evolution: the color, size, or shape of the area or mole may change over time.
Melanoma can be cured if it is diagnosed early and treated when the tumor is thin and has not deeply invaded the skin. However, if a melanoma is not removed at its early stages, cancer cells may grow downward from the skin surface, invading healthy tissue. When a melanoma becomes thick and deep, the disease often spreads to other parts of the body and is difficult to control.
Diagnosis of Skin Cancer
Doctors should check the skin during a routine physical exam, and dermatologists are specially trained to do this check. People who have already had skin cancer, or are at high risk, should be sure to have regular exams. When an area of skin does not look normal, the doctor may remove all or part of the growth using a local anesthetic so it is not painful. This is procedure is called a biopsy. The tissue is examined to check for cancer cells.
- Nonmelanoma skin cancer: Because basal cell carcinomas and squamous cell carcinomas rarely spread beyond the skin, a biopsy and microscopic examination often is the only test needed.
- Melanoma: If your doctor suspects you have melanoma, you may have additional biopsies or imaging tests. The entire area will be removed if possible. The doctors may categorize the cancer using Stages I to IV based upon whether the cancer has spread to other parts of the body. Knowing the stage of a skin cancer helps to determine the best treatment plan. The nearby lymph nodes in the area may be checked, and may need to be removed.
The cure rate for skin cancer is very high if detected early. It is important to examine the skin regularly to check for new growths or other changes in the skin. Any new, colored growths or any changes in growths that are already present should be reported to a doctor without delay.
What Treatments Are Used for Actinic Keratosis?
Actinic keratoses (precancerous lesions) have a variety of treatment options based upon the extent of lesions:
- Freezing (cryotherapy) with liquid nitrogen is most commonly used to treat actinic keratoses. This takes only a few minutes. The area sloughs off, allowing new skin growth. Side effects may include blisters, skin redness, and changes in skin texture or color at the site of treatment. These spots usually clear up in a week or two.
- Electrodesiccation and curettage (ED&C): after numbing, the precancerous area is surgically scraped with a spoon-shaped tool and then treated with an electric current to control bleeding. A white scar may occur.
- Topical creams may also be used, especially if there are several areas to treat. Redness, peeling or a slight burning sensation may occur for a few weeks. Scarring is uncommon.
- Photodynamic therapy involves the application of a chemical solution and exposure of the area to artificial light to destroy the damaged skin cells. Side effects may include redness, peeling, swelling, scarring or a burning sensation during therapy.
Actinic Keratosis Treatments
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|diclofenac gel||Voltaren, Solaraze|
|fluorouracil topical||Carac, Efudex, Fluoroplex, Tolak|
|ingenol mebutate gel||Picato|
How to Treat Nonmelanoma Skin Cancer
Treatment of non-melanoma skin cancers like basal cell skin cancer or squamous cell skin cancer usually involves some type of surgery; often this a minor surgical procedure. Your treatment will depend upon the type of skin cancer you have, if it has spread, and your health conditions and age.
Common surgical procedures include:
- Biopsy/surgery: Many skin cancers can be cut from the skin quickly and easily, during an in-office procedure. In fact, the cancer is sometimes completely removed at the time of the biopsy, and no further treatment is needed. Sometimes a wider excision is needed. A margin of healthy tissue will also be removed.
- Electrodesiccation and curettage (ED&C): involves numbing the area with a local anesthetic and scooping the skin cancer out with a sharp spoon shaped instrument called a curette. The area is then treated with an electric current from a special machine (a procedure called electrodesiccation) to control bleeding and kill any cancer cells remaining around the edge of the wound. Most patients develop a flat white scar.
- Mohs Surgery: is a type of outpatient surgery performed by a specialist. The aim is to remove all of the cancerous tissue and as little of the healthy tissue as possible, and is particularly useful when the shape and depth of the tumor is unknown. This method is also used to remove large tumors, those in hard-to-treat places like on the face or lips, and cancers that have recurred. The procedure is performed under local anesthetic, and the cancer is shaved off one thin layer at a time. Each layer is checked under a microscope until the entire tumor is removed. The degree of scarring depends on the location and size of the treated area.
Learn more: Mohs Surgery Overview
- Cryosurgery: the use of cold to freeze and kill the abnormal cells. Liquid nitrogen is used to treat precancerous skin conditions such as actinic keratosis, and certain small skin cancers. After the area is thawed, the dead tissue falls off. More than one treatment may be necessary to remove the growth completely. Pain and swelling may be present after the area thaws, and a white scar may form in the treated area.
- Skin Grafts: often needed to close the wound and reduce the amount of scarring, especially if a large cancer is removed. The procedure involves taking a piece of healthy skin from another part of the body to replace the skin that was removed. This may also be done in Moh's surgery.
Other options to treat non-melanoma skin cancer include:
- Laser Therapy: uses a narrow beam of light to remove or destroy cancer cells. This procedure is sometimes used for cancers that only involve the outer layer of skin.
- Radiation Therapy: uses high-energy rays to kill cancer cells. This treatment is often used for cancers in areas that are difficult to treat with surgery (example eyelid, the tip of the nose, or the ear). Several treatments may be necessary. Radiation therapy may cause a rash or make the skin in the area dry or red. Changes in skin color or texture may develop after the treatment, and may become more noticeable many years later.
- Topical Chemotherapy is the use of anticancer drug in a cream or lotion applied to the skin.
- Other Medications: Nonmelanoma cancers that have spread to other areas of the body, recur, or that have not responded to prior treatments may be treated with certain systemic (oral or injection) medications.
Basal Cell Carcinoma Treatments
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Squamous Cell Carcinoma Treatments
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How is Melanoma Treated?
The standard treatment for melanoma is removal with surgery (excision). A wide local excision may be needed, removing some normal tissue (the margin) around the melanoma, to lower the chance that any cancer is left and that it will recur. In cases where the melanoma is very thin, enough tissue is often removed during the biopsy, and no further surgery is necessary. For thick melanomas, it may be necessary to do a wider excision to take out a larger and deeper margin of tissue. Where large areas of tissue are removed, a skin graft may be performed. Stitches are carefully placed but a scar will occur in most cases.
Lymph nodes near the tumor may also be evaluated and removed during surgery. If cancer cells are found in the lymph nodes, it may mean that the melanoma cells have spread to other parts of the body.
What is a Sentinel Lymph Node Biopsy?
A sentinel lymph node biopsy may be performed during melanoma surgery. This will reduce the number of lymph nodes that need to be removed for biopsy. The procedure involves injecting a blue dye or a small amount of radioactive material near the area where the tumor was. This material flows into the sentinel lymph nodes, the first lymph nodes that the cancer is likely to spread to from the primary tumor.
A surgeon then looks for the dye or uses a scanner to find the sentinel lymph nodes and then removes it for examination by a pathologist. If the sentinel lymph node biopsy is positive for cancer cells, then the rest of the surrounding lymph nodes are usually removed. If the biopsy is negative, the remaining lymph nodes do not need to be removed as the melanoma has not spread to these areas.
For some people, treatment will involve radiation therapy, immunotherapy, targeted drug therapy, chemotherapy or a combination of these. Your treatment will depend upon the type of skin cancer you have, if it has spread, and your health conditions and age.
Learn More: What is Radiation Therapy?
Treatment Options for Metastatic Melanoma
Surgery is generally not effective in curing melanoma that is known to have spread to other parts of the body such as the lungs or the brain (metastatic melanoma). However, surgery may still be done to help control the spread of the cancer, lessen symptoms, and improve survival. In such cases, doctors may use other methods of treatment, such as:
- Immunotherapy: Drugs that stimulate the immune system to fight the cancer.
- Targeted drug treatment: Drugs that act on specific molecules that are needed by the cancer cells.
- Chemotherapy: Drugs that interfere with cancer cell growth or reproduction.
- Radiation therapy: Using external radiation to kill cancer cells.
- A combination of any of these methods
When therapy is given after surgery to remove all cancerous tissue, the treatment is called adjuvant therapy. The goal of adjuvant therapy is to kill any undetected cancer cells that may remain in the body.
Immunotherapy is a newer form of treatment that uses the body's immune system to fight the melanoma. The immune checkpoint inhibitors:
are used in melanoma; sometimes they are used in combination. Keytruda and Opdivo are PD-1 inhibitors and Yervoy is known as a CTLA-4 inhibitor, and they help to strengthen our immune response to cancer.
These drugs are given as an injection in the vein, and have a wide variety of side effects, some of which may be serious. However, these treatments have been shown to decrease the spread of the tumor as well as lengthen survival against advanced melanoma.
Nivolumab is given once every 2 weeks, and pembrolizumab is given once every 3 weeks. These treatments are usually continued unless the melanoma progresses or side effects become intolerable. Ipilimumab is given every once every 3 weeks for 4 doses total. Ipilimumab may be combined with nivolumab for advanced melanoma treatment (see study below).
Side Effects with the Immune Checkpoint Inhibitors
Side effects with the PD-1 inhibitors (nivolumab, pembrolizumab) can include cough, tiredness, nausea, skin rash, lack of appetite, constipation, diarrhea and muscle aches. Side effects with the CTLA-4 inhibitor (ipilimumab) can include fatigue, itching, skin reactions, and diarrhea, and colitis.
Serious side effects with immunotherapy, both PD-1 inhibitors and CTLA-4 inhibitors, have included immune-mediated side effects such as inflammatory reactions of the lungs, skin, liver, or kidneys, where the body attacks its own tissues. The use of high dose corticosteroids can be used to control this side effect, usually without interfering with the immunotherapy.
Immunotherapy is also being used in combination with good outcomes. In January, 2016, Bristol-Myers Squibb reported that the FDA approved Opdivo (nivolumab) in combination with Yervoy (ipilimumab) for the treatment of patients with BRAF V600 wild-type and BRAF V600 mutation-positive unresectable or metastatic melanoma.
In October 2017, Wolchok and colleagues published a study in the New England Journal of Medicine (NEJM) that detailed 3-year overall survival outcomes from the Checkmate-067 trial. Significantly longer overall survival occurred with the combination of nivolumab (Opdivo) plus ipilimumab (Yervoy) or with nivolumab alone than with ipilimumab alone in advanced melanoma. The overall survival rate at 3 years was 58% in the nivolumab-plus-ipilimumab group and 52% in the nivolumab group, as compared with 34% in the ipilimumab group. At a minimum follow-up of 36 months, the median overall survival had not yet been reached in the nivolumab-plus-ipilimumab group, and was 37.6 months in the nivolumab group, as compared to 19.9 months in the ipilimumab group, a statistically significant effect. The safety profile remained as seen in other studies, but a greater percentage of side effects (59%) occurred in the nivolumab-plus-ipilimumab group, compared to the nivolumab group (21%) or the ipilimumab group (28%).
Other agents that may be used to help boost the immune system in the treatment against melanoma include:
- Cytokines: (interferon-alfa 2b [Intron A], PEG-interferon [Peg-Intron], and interleukin-2)
- Talimogene laherparepvec (Imlygic) - an oncolytic virus
- BCG Vaccine (TheraCys, Tice BCG Live [for intravesical use], Tice BCG Vaccine)
Targeted Drug Therapy
Targeted therapy blocks a specific gene mutation found in some melanomas called BRAF. About 50% of melanomas contain a BRAF gene. Using a targeted drug to block a protein made by BRAF genes can help to shrink the melanoma.
Targeted drug therapy includes:
- the BRAF inhibitors vemurafenib (Zelboraf) and dabrafenib (Tafinlar)
- the MEK inhibitors trametinib (Mekinist) and cobimetinib (Cotellic).
These drugs, also called kinase inhibitors, are usually used in combination (dabrafenib + trametinib or vemurafenib + cobimetinib) for greatest effect, can lengthen the time until the cancer starts to grow, and may extend survival, too.
These drugs are all taken by mouth, either once or twice a day. Side effects with targeted drugs can include skin reactions, fatigue, fever, blurred vision or other change in vision, and liver toxicity, among many other side effects.
Chemotherapy is the use of one or more drugs to kill cancer cells. It is generally a systemic therapy, meaning that it can affect cancer cells throughout the body. The use of checkpoint inhibitors and targeted therapy have largely replaced the use of older chemotherapy drugs for melanoma treatment, although they still may be used. Chemotherapy is usually given in cycles: a treatment period followed by a recovery period, then another treatment period, and so on.
Agents such as dacarbazine (DTIC-Dome) and temozolomide (Temodar) are chemotherapy agents used in metastatic melanoma. Immunotherapy is often selected first over chemotherapy today because these agents are better tolerated and have a greater affect in treating the cancer.
Side effects from chemotherapy depend largely on the specific drugs and the dose (amount) of drug given. Common side effects of chemotherapy include nausea and vomiting, hair loss, mouth sores, and fatigue.
Oncolytic Virus Immunotherapy
Talimogene laherparepvec (Imlygic) is used to treat melanoma when it is on the skin or in the lymph glands, but can't be removed with surgery. Imlygic is a genetically modified weak herpes simplex virus, the same virus that cause cold sores. The medication is injected every 2 weeks directly into the melanoma tumor.
Common side effects with Imlygic can include flu-like symptoms such as fevers and chills, fatigue, nausea, and pain at the injection site.
Radiation therapy is the use of high-energy rays to kill cancer cells. In some cases, radiation therapy is used to shrink the tumor to help relieve some of the symptoms caused by melanoma, such as bone pain. Radiation therapy is most commonly used to help control melanoma that has spread to the brain, bones, and other parts of the body.
Side effects of radiation therapy depend mainly on the part of the body that is treated and the treatment dose. Common side effects of radiation therapy include fatigue, skin changes, and hair loss in the treated area.
Metastatic Melanoma Treatments
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Merkel cell carcinoma is a rare type of skin cancer that usually appears as a flesh-colored or bluish-red nodule, often on your face, head or neck. It is an aggressive, fast-growing type of skin cancer. Merkel cell carcinoma most frequently develops in older people. Long-term sun exposure or a weak immune system may increase your risk of developing Merkel cell carcinoma. Treatment options for Merkel cell carcinoma often depend on whether the cancer has spread beyond the skin. Bavencio (avelumab), a PD-L1 blocking antibody, is a recently approved immunotherapy for treatment of Merkel cell carcinoma.
Merkel Cell Carcinoma Treatments
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What to Expect After Skin Cancer Surgery
The side effects of surgery depend mainly on the size and location of the tumor and the extent of the operation. Surgery that involves only local removal may be all that is needed. More extensive cancer, like metastatic melanoma, may require continued drug treatments after surgery for months or even years to lessen tumor growth and prolong survival.
Pain and discomfort after surgery can be controlled with pain relieving medicine. It is also common for patients to feel tired or weak for a while. The length of time it takes to recover from an operation varies for each patient. Scarring may also be a concern for some patients. Ask your doctor about scarring and how to minimize it.
How Do I Prevent Skin Cancer?
You can help to prevent skin cancer by protecting your skin from the harmful UV rays of the sun. Follow these guidelines to help prevent skin cancer.
- Whenever possible, you should avoid exposure to the strongest sun of the day (usually from 10 AM to 4 PM), but remember you can still burn even on cloudy days.
- Wear protective clothing, such as a sun hat and long sleeves. Wearing clothes that help to block out the sun's harmful rays can help to prevent skin cancer. Ask your dermatologist if UV protective clothing is helpful for you.
- Sunscreens with a sun protection factor (SPF) of 30 or higher can help to prevent sunburn, but re-application is needed, especially if swimming or sweating.
- Always follow the label directions for use and reapplication of sunscreens, especially if sweating or swimming.
- It may be better to use lotions and creams that you apply, than sunscreen sprays, for more complete coverage.
- See your primary care doctor or dermatologist at regular recommended intervals to have your skin checked for cancers or pre-cancerous lesions.
- Parents should play an active role in protecting their infants and children from sunburns, and educate them about the sun's risk and protective measures.
- Do a skin self-exam each month; see your doctor if you see changes in your skin.
How Is a Skin Self-Exam Done?
By checking your skin regularly, you will become familiar with what is normal for you and pick up skin changes more quickly. The best time to do a skin self-exam is after a shower or bath. The skin should be checked in a well-lit room using a full-length mirror and a hand-held mirror. It's best to begin by learning where birthmarks, moles, and blemishes are and what they usually look and feel like. Check for anything new, especially a change in the size, shape, texture, or color of a mole or a sore that does not heal. Follow these steps:
- Check yourself from head to toe. Don't forget to check all areas of the skin, including the back, the scalp, between the buttocks, and the genital area:
- Look at the front and back of your body in the mirror, then raise your arms and look at your left and right sides.
- Bend your elbows and look carefully at your fingernails, palms, forearms (including the undersides), and upper arms.
- Examine the back, front, and sides of your legs. Also look between the buttocks and around the genital area.
- Sit and closely examine your feet, including the toenails, the soles, and the spaces between the toes.
- Look at your face, neck, ears, and scalp. You may want to use a comb or a blow dryer to move hair so that you can see better.
It may be helpful to record the dates of your skin exams and to write notes about the way your skin looks. Having a partner or close family member help you examine can be a good idea for areas that are hard to see, such as your back or in your hair. If you find anything unusual, see your doctor right away.
- American Cancer Society: Cancer Facts and Figures 2017. Atlanta, Ga: American Cancer Society, 2017. Accessed at https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2017/cancer-facts-and-figures-2017.pdf
- Firnhaber J. Diagnosis and Treatment of Basal Cell and Squamous Cell Carcinoma. Am Fam Physician. 2012 Jul 15;86(2):161-168. Accessed at http://www.aafp.org/afp/2012/0715/p161.html
- Sosman JA. Atkins MB. Ross E. Patient education: Melanoma treatment; advanced or metastatic melanoma (Beyond the Basics). Up To Date. Accessed December 7, 2017 at https://www.uptodate.com/contents/melanoma-treatment-advanced-or-metastatic-melanoma-beyond-the-basics
- Sosman JA. Atkins MB. Ross E. Patient education: Melanoma treatment; localized melanoma (Beyond the Basics). Up To Date. Accessed December 7, 2017 at https://www.uptodate.com/contents/melanoma-treatment-localized-melanoma-beyond-the-basics
- Skin Cancer (Including Melanoma)—Patient Version. National Cancer Institute. Accessed December 7, 2017 at https://www.cancer.gov/types/skin
- Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. N Engl J Med. 2017 Oct 5;377(14):1345-1356. Accessed December 7, 2017 at https://www.ncbi.nlm.nih.gov/pubmed/28889792
- Bristol-Myers Squibb’s Opdivo (nivolumab) + Yervoy (ipilimumab) Regimen Receives Expanded FDA Approval in Unresectable or Metastatic Melanoma Across BRAF Status. Drugs.com Jan 23, 2016. Accessed December 7, 2017 at https://www.drugs.com/newdrugs/bristol-myers-squibb-s-opdivo-nivolumab-yervoy-ipilimumab-regimen-receives-expanded-fda-approval-4332.html
- BMS Receives FDA Approval for Opdivo (nivolumab) + Yervoy (ipilimumab) Regimen in BRAF V600 Wild-Type Melanoma. Drugs.com. October 1, 2015. Accessed December 7, 2017 at https://www.drugs.com/newdrugs/bms-receives-fda-approval-opdivo-nivolumab-yervoy-ipilimumab-regimen-braf-v600-wild-type-melanoma-4271.html
- FDA Approves Expanded Indication for Keytruda (pembrolizumab) for the Treatment of Patients with Advanced Melanoma. Drugs.com. December 18, 2015. Accessed December 7, 2017 at https://www.drugs.com/newdrugs/fda-approves-expanded-indication-keytruda-pembrolizumab-patients-advanced-melanoma-4319.html
- Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373(1):23-34.
- American Cancer Society. Melanoma Skin Cancer. Accessed December 7, 2017 at http://www.cancer.org/acs/groups/cid/documents/webcontent/003120-pdf.pdf.
- American Cancer Society. Treating Melanoma Skin Cancer. May 2016. Accessed December 7, 2017 at https://www.cancer.org/content/dam/CRC/PDF/Public/8826.00.pdf