FDA Approved Drugs for Melanoma

In this section, learn about FDA (U.S. Food and Drug Administration) approved drugs for melanoma, as well as suggestions for managing the side effects associated with these drugs.

FDA-Approved Drugs

DTIC (dacarbazine)

Purpose: DTIC is given to shrink or slow the growth of melanoma tumors that have spread throughout the body.

How it works: DTIC is a chemotherapy drug, specifically an alkylating agent. It interferes with the growth of cancer cells. Currently, DTIC is the only FDA approved chemotherapy drug for the treatment of metastatic melanoma.

Which patients: Patients with Stage IV melanoma

How it is given: DTIC is given intravenously for 10 days. The treatment may be repeated every 4 weeks. Alternatively, the drug can be given at an accelerated dose for 5 days, with the treatment repeated every 3 weeks.

Effectiveness: DTIC response rates are in the 6% to 20% range, and the response lasts about 6-8 months. DTIC has not been shown to improve progression-free or overall survival.

Side effects: Side effects depend on the individual and the dose used but can include the following:

  • Allergic reactions, including shortness of breath, throat closing, swelling of lips, face, or tongue, or hives
  • Decreased bone marrow function and blood problems (extreme fatigue, easy bruising or bleeding, black, bloody or tarry stools, or fever, chills, or signs of infection)
  • Nausea, vomiting, diarrhea, or loss of appetite
  • Temporary hair loss
  • Flu-like symptoms including fever, muscle and joint pain.

DTIC has also been associated with the development of other cancers (secondary malignancy). It also can harm the liver.

References:
Serrone L, Zeuli M, Sega FM, Cognetti F. Dacarbazine-Based Chemotherapy for Metastatic Melanoma: Thirty-Year Experience Overview. J Exp Clin Cancer Res. 2000;19(1):21-34.

INTRON A (high-dose interferon alfa-2b)

Purpose: High-dose interferon is given to rev up the immune system in order to kill melanoma cells. Interferon is given to prevent the cancer from coming back after initial therapy, such as surgery.

How it works: Interferon is a naturally occurring protein that fights viral infections and other diseases. While the drug’s main function is to alert the immune system to kill the melanoma cells, its mechanism is not completely understood. It is possible that it also chokes the blood supply to the tumor (antiangiogenesis) and directly fights the tumor growth.

Which patients: Intron A is given in the adjuvant setting after surgery to Stage III patients who are free of disease but are at a high risk of the disease returning. It is also given to certain late Stage IIB or Stage IIC patients (those with lesions of Breslow thickness > 4 mm).

How it is given: Intron A can be given intravenously, intramuscularly, subcutaneously, or intralesionally.

In the United States, Intron A is usually given in a 2-phase process over a 1-year period. In the induction phase, Intron A is given intravenously in a hospital or an office setting at the maximum tolerated dose, which is 5 days a week for 4 weeks. Each injection takes about 20-30 minutes. During the maintenance phase, Intron A is given subcutaneously 3 times a week for the remainder of the year. Most often, patients can do these injections themselves.

There have also been studies using low-dose Intron A. In these studies, there was a subcutaneous induction phase for 1-3 weeks followed by a maintenance phase for 3 times a week for a period of 1-3 years.

Effectiveness: When compared with patients who had no adjuvant treatment (treatment following surgery), Intron A was effective at preventing melanoma relapse. It extended the relapse free period from 0.98 years to 1.72 years. Five year-survival was 46% for those who took the drug compared to 37% for those who did not.

Side effects: Interferon is associated with a variety of side effects:

    • Acute flu-like symptoms occur typically within 4-8 hours of injection (fever, chills, muscle pain, headache, nausea, vomiting). These are often worst at the beginning of treatment but then improve with time.

Important: Stay hydrated during the acute phase, and you may want to take a fever-lowering drug to relieve some of the flu symptoms, if your doctor advises. Keep warm with plenty of warm blankets.

Important: Some techniques to fight fatigue include:

  • Try to be active. Balance your activity with rest, and plan activity for times when you feel well
  • Get as much sleep as you can
  • Eat a balanced diet with lots of fruits and vegetables
  • Drink plenty of water

Other side effects include:

  • Low white blood cell and red blood cell counts (as recorded before, during, and at the completion of treatment)
  • Liver damage (depending on severity, a potential signal to discontinue treatment)
  • Depression is common, occurring in about 40% of patients in the main trial. A small percentage of patients, approximately 2%, attempt suicide or develop suicidal ideas.

Important: Be aware of the potential seriousness of depression and call 911 if you think you may harm yourself or anyone else. Your physician may screen you for depression at the beginning and throughout your treatment to determine if you need a dose reduction or need to be taken off treatment. If you have any history of depression or any psychiatric history, tell your physician.

  • Loss of appetite (resulting in weight loss). This may result from nausea and vomiting or altered taste.

Important:

  • Eat smaller portions and have healthy snacks in between
  • Avoid greasy and spicy foods
  • If cooking smells make you sick, try eating foods cold.
  • If you have a metallic taste in your mouth, get some tart liquids such as lemonade or orange juice. Use plastic rather than metallic utensils. Eat fresh foods rather than canned foods.
  • Lessened attention/memory. This may interfere with your ability to take the drug and perform certain tasks.

Other points about side effects:

As with any treatment, the side effects of interferon therapy depend on the prescribed dose. Low-dose therapy is often well tolerated, while high-dose therapy tends to produce more severe and consistent side effects. Often, the most severe side effects occur during the first few weeks of therapy and then taper off significantly.

If the symptoms or signs are significantly abnormal, the treatment may be interrupted for a time and then resumed at a lower dose. Throughout the course of the therapy, treatment may be stopped and restarted at different dosages as needed.

If you are having severe side effects, talk to your doctor. Treatments are available to relieve symptoms such as nausea and fatigue. You will also receive careful and continuous monitoring for life-threatening side effects, including bone marrow suppression and liver damage. Many side effects are generally reversible when therapy is stopped.

Additional information/resources:

Patient assistance: ACT program. 1-866-363-6379 http://www.merck.com/merckhelps/act-program/home.html

KEYTRUDA (pembrolizumab)

Purpose: Keytruda is a humanized monoclonal antibody. It is designed to block a cellular target known as PD-1, which restricts the body’s immune system from attacking melanoma cells.

How it works: Keytruda is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to fight advanced melanoma. Keytruda blocks the interaction between PD-1 and its lignds, PD-L1 and PD-L2, and may affect both tumor cells and healthy cells.

Which patients: Keytruda is approved for patients with unresectable Stage III melanoma (melanoma that cannot be completely removed by surgery) or Stage IV melanoma, after they have progressed on ipilimumab and, if they the carry the BRAF 600 mutation, after they have progressed on a BRAF inhibitor.

How it is given: Keytruda is given intravenously, each 2 mg/kg dose is given over a 30-minute period, usually every 3 weeks until there is disease progression or unacceptable side effects. It is given in an outpatient clinic and does not require hospitalization.

Effectiveness: In a large Phase 1 clinical trial, half of the participants received Keytruda at the recommended dose of 2 mg/kg. Of these patients, approximately 24 percent had their tumors shrink. This effect lasted at least 1.4 to 8.5 months and continued beyond this period in most patients. A similar percentage of patients had their tumor shrink at the 10 mg/kg dose.

An improvement in survival or disease-related symptoms has not yet been established. Merck is currently conducting ongoing Phase 2 and 3 clinical studies in advanced melanoma patients.

Side effects: Although it is not common, Keytruda can cause your immune system to attack normal organs and tissues in many areas of your body and can affect the way they work. These problems can sometimes become serious or life-threatening.
Call or see your doctor right away if you develop any symptoms of the following problems or these symptoms get worse:

  • Lung problems (pneumonitis). Symptoms of pneumonitis may include:
    • shortness of breath
    • chest pain
    • new or worse cough
  • Intestinal problems (colitis) that can lead to tears or holes in your intestine. Signs and symptoms of colitis may include:
    • diarrhea or more bowel movements than usual
    • stools that are black, tarry, sticky, or have blood or mucus
    • severe stomach-area (abdomen) pain or tenderness
  • Liver problems (hepatitis). Signs and symptoms of hepatitis may include:
    • yellowing of your skin or the whites of your eyes
    • dark urine
    • nausea or vomiting
    • feeling less hungry than usual
    • pain on the right side of your stomach area (abdomen)
    • bleeding or bruising more easily than normal
  • Hormone gland problems (especially the thyroid, pituitary, and adrenal glands). Signs and symptoms that your hormone glands are not working properly may include:
    • rapid heart beat
    • weight loss
    • increated sweating
    • weight gain
    • hair loss
    • feeling cold
    • constipation
    • your voice gets deeper
    • muscle aches
    • dizziness or fainting
    • headaches that will not go away or unusual headache
  • Kidney problems, including nephritis and kidney failure. Signs of kidney problems may include:
    • change in the amount or color of your urine.
  • Problems in other organs.
    • rash
    • changes in eyesight severe or persistent muscle or joint pains
    • severe muscle weakness
    The following are the most common side effects (>_20):

  • fatigue
  • cough
  • nausea
  • severe Itching
  • rash
  • decreased appetite
  • constipation
  • joint pain
  • diarrhea

Patient assistance: Patients can call 1-855-257-3932 or visit www.merckaccessprogram-keytruda.com

OPDIVO (nivolumab)

Purpose: Opdivo is a humanized monoclonal antibody. It is designed to block a cellular target known as PD-1, which results in an anti-tumor immune response.

How it works: Opdivo is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to fight advanced melanoma. Opdivo blocks the interaction between PD-1 and its ligands PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response.

Which patients: Opdivo is approved for patients with unresectable Stage III melanoma (melanoma that cannot be completely removed by surgery) or Stage IV melanoma, after they have progressed on ipilimumab and, if they carry the BRAF V600 mutation, after they have progressed on a BRAF inhibitor.

How it is given: Opdivo is given intravenously, with each 3 mg/kg dose given over a 60-minute period every 2 weeks, until disease progression or unacceptable side effects.  It is given in an outpatient clinic and does not require hospitalization.

Effectiveness: The approval of Opdivo was based on the results of a Phase III clinical trial of 120 patients with unresectable (cannot be removed by surgery) or metastatic (advanced) melanoma. Of these patients 32 percent had a response to Opdivo. This effect lasted for more than six months in approximately one-third of the patients. Responses to Opdivo were demonstrated in both patients with and without the BRAF V600 mutation.

This indication was approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Side effects: Although it is not common, Opdivo can cause your immune system to attack normal organs and tissues in many areas of your body and can affect the way they work. These problems can sometimes become serious or life-threatening. Call or see your doctor right away if you develop any symptoms of the following problems or these symptoms get worse.

Important: Call or see your healthcare provider right away if you develop any symptoms of the following problems or these symptoms get worse:

  • Lung problems (pneumonitis). Symptoms of pneumonitis may include:
    • New or worsening cough
    • Chest pain
    • Shortness of breath
  • Intestinal problems (colitis) that can lead to tears or holes in your intestine. Signs and symptoms of colitis may include:
    • Diarrhea (loose stools) or more bowel movements than usual
    • Blood in your stools or dark, tarry, sticky stools
    • Severe stomach area (abdomen) pain or tenderness
  • Liver problems (hepatitis). Signs and symptoms of hepatitis may include:
    • Yellowing of your skin or the whites of your eyes
    • Severe nausea or vomiting
    • Pain on the right side of your stomach-area (abdomen)
    • Drowsiness
    • Dark urine (tea colored)
    • Bleeding or bruise more easily than normal
    • Feeling less hungry than usual
  • Kidney problems, including nephritis and kidney failure. Signs of kidney problems may include:
    • Decrease in the amount of urine
    • Blood in your urine
    • Swelling in your ankles
    • Loss of appetite
  • Hormone gland problems (especially the thyroid, pituitary, and glands). Signs and symptoms that your hormone glands are not working properly may include:
    • Headache that will not go away or unusual headaches
    • Extreme tiredness
    • Weight gain or weight loss
    • Changes in mood or behavior, such as decreased sex drive, irritability or forgetfulness
    • Dizziness or fainting
    • Hair loss
    • Feeling cold
    • Constipation
    • Voice gets deeper
  • Problems in other organs. Signs of these problems include:
    • Rash
    • Changes in eyesight
    • Severe or persistent muscle or joint pains
    • Severe muscle weakness

The most common adverse reaction (reported in at least 20% of patients) was rash.

Additional information/resources:

Patient assistance: 1-800-861-0048 (hours: 8 am – 8 pm est.) or  www.bmsaccesssupport.com 

MEKINIST (trametinib)

Purpose: Mekinist blocks a cellular pathway to stop the growth of melanoma tumors.

How it works: Mekinist is a kinase inhibitor that blocks the activity of the V600E or V600K mutated form of BRAF, a key protein that helps cancer cells grow. About half of patients with melanoma have this mutated form of the protein in their tumors.

Which patients: Mekinist is FDA-approved for patients who carry the BRAF V600E or V600K mutation and who have unresectable Stage III melanoma (melanoma that cannot be removed surgically) or Stage IV melanoma. Before receiving Mekinist, patients must test positive for the BRAF mutation. Mekinist cannot be used by patients who have already used another BRAF inhibitor.

How it is given: Mekinist is an oral drug. Patients receive 2 mg orally once daily.

Effectiveness: In a large phase III clinical trial comparing Mekinist to chemotherapy, progression-free survival (the time a patient lives without cancer growing or spreading) was 4.8 months for patients on Mekinist versus 1.5 months for patients on chemotherapy.

When Mekinist was compared to chemotherapy, 22% of all patients treated with Mekinist experienced tumor shrinkage compared to 8% for chemotherapy.

Side effects:

  • Heart problems, including heart failure, occur in approximately 16% of patients. Signs and symptoms of heart problems include:
    • Feeling like your heart is pounding
    • Shortness of breath
    • Swelling of ankles or feet
    • Feeling lightheaded

Important: You should have your heart function checked before you start taking Mekinist and while you are being treated.

  • Eye problems, including blindness, occurred in about 1% of patients. Signs and symptoms of eye problems include:
    • Blurred vision, loss of vision, or other vision problems
    • Halo (seeing blurred outline around objects)

Important: Tell your doctor immediately if any of these symptoms appear.

  • Lung or breathing problems occurred in under 2% of patients. Signs and symptoms of lung or breath problems include:
    • Shortness of breath
    • Cough
  • Skin rash is the most common side effect of Mekinist occurring in 87% of all patients. In some cases it can be severe enough to cause hospital admission. Tell your doctor if you get any of these symptoms:
    • Skin rash
    • Acne
    • Redness, swelling, peeling, or tenderness of hands or feet
    • Skin redness
  • High Blood Pressure may occur or get worse while taking Mekinist. You should have your blood pressure checked while taking Mekinist. Tell your doctor if you get any of these symptoms:
    • Severe headache
    • Lightheadness
    • Dizziness

Other side effects may include:

  • Diarrhea
  • Swelling of the face, arms, or legs

Additional information/resources:

Patient assistance: Patients can call 1-8ONCOLOGY1 (1-866-265-6491)

MEKINIST (trametinib) and TAFINLAR (dabrafenib) Combo

Purpose: Mekinist in combination with Tafinlar blocks a cellular pathway to inhibit the growth of melanoma metastases.

How it works: Tafinlar is an inhibitor of some mutated forms of BRAF kinases. Mekinist is an inhibitor of some MEK kinases. Both of these kinases are key proteins that help melanoma cells grow. About half of all patients with melanoma have a mutated form of the BRAF protein in their tumors.

Which patients: Mekinist in combination with Tafinlar is indicated for the treatment of adult patients with unresectable Stage III melanoma (melanoma that cannot be removed by surgery) or Stage IV melanoma (metastatic melanoma) with BRAF V600 E or V600 K mutations. Before starting treatment the patient should test positive for the presence of a BRAF V600E or V600K mutation.

How it is given: Tafinlar is an oral drug. Patients receive 150 mg orally twice daily. Mekinist is also an oral drug and patients receive 2mg once daily.

Effectiveness: In a Phase III trial that compared the trametinib and dabrafenib combination to vemurafenib, at 12 months the overall survival in the combination arm was 72% versus 65% in the vemurafenib arm.

Progression-free survival (the time a patient lives without cancer growing or spreading) was 11.4 months for patients treated with the trametinib and dabrafenib combination, versus 7.3 months for patients treated with vemurafenib.

Side effects: Several side effects are common in the course of treatment. Most of these side effects are mild or moderate, although there have been some severe side effects. These side effects can usually be managed with either a decrease in the dosage or by briefly stopping one or both of the drugs and then resuming after the symptoms improve. Sometimes, when the drug or drugs are resumed, it is at a lower dosage.

  • New Skin Cancers
    • For patients treated with Mekinist in combination with Tafinlar, the incidence of Cutaneous Squamous Cell Carcinoma was 7% compared with 19% in patients treated with Tafinlar alone. The incidence of basal cell carcinomas was higher (9% compared with 2%) for Mekinist in combination with Tafinlar.
  • New Primary Melanomas: they occur in approximately 2% of patients.
    • If these lesions appear, they should be removed, but typically you can continue taking the drug without changing the dosage.

Important: You should have a dermatologic examination before you start these medicines, and every two-three months while you remain on the drugs, up to 6 months after you stop taking the drugs.

  • Serious Fevers: 26% of all patients developed fevers when treated with Tafinlar alone. In 2% of these patients these fevers were serious and were accompanied by one or more additional symptoms. For patients treated with Mekinist in combination with Tafinlar, the incidence of fever was 71%, while 25% had other associated symptoms such as:
    • Low Blood Pressure
    • Chills
    • Dizziness
    • Too much fluid loss (dehydration)
    • Kidney problems

Important: Tell your doctor immediately if you get a fever.

  • Skin rash is the most common side effect, occurring in 65% of all patients taking Mekinist in combination with Tafinlar. In some cases it can be severe enough to cause hospital admission. Tell your doctor if you get any of these symptoms:
    • Skin rash
    • Acne
    • Blistering
    • Redness, swelling, peeling, or tenderness of hands or feet
    • Skin redness
  • Hemorrhage: 16% of all patients had a hemorrhagic event (including accumulation of blood within the brain) and in 4% of cases it was fatal.
  • Blood Clots: 7% of all patients had a blood clot in a vein (deep vein thrombosis) or in the lung (pulmonary embolism). One patient died of a pulmonary embolism (2% of patients).

Important: Immediately seek medical attention if you experience any concerning symptoms, including but not limited to; shortness of breath, chest pain, leg swelling, bleeding or confusion.

  • Heart problems, including heart failure, occurred in approximately 9% of patients. Signs and symptoms of heart problems include:
    • Feeling like your heart is pounding
    • Shortness of breath
    • Swelling of ankles or feet
    • Feeling lightheaded

Important: You should have your heart function checked before you start taking Tafinlar in combination with Mekinist as well as during treatment.

  • Blood Sugar Problems (diabetes): Some people may develop high blood sugar, or if they have diabetes it may get worse. Tell your doctor if you have any of the following symptoms:
    • Increased thirst
    • Urinating more than usual
    • Your breath smells like fruit
  • Eye problems such as uveitis, retinal vein occlusion, and Retinal Pigment Epithelial Detachment occurred very rarely in patients. Symptoms include eye pain, swelling or redness, blurred vision, floaters, or sudden loss of vision.

Important: You should have your eyes examined before and while you are taking these medicines. Tell your doctor immediately if any eye symptoms appear.

Additional information/resources:
Patient assistance: Patients can call 1-8ONCOLOGY1 (1-866-265-6491)

PROLEUKIN (IL-2 / Interleukin 2)

Purpose: IL-2 is an immunotherapy that uses the body’s natural immune system to fight melanoma.

How it works: IL-2 is a recombinant form of interleukin-2 (IL-2), a cytokine which helps activate the immune system (including T cell and natural killer cells) to kill cancer cells.

Which patients: IL-2 is approved for the treatment of advanced metastatic melanoma. Patients who receive IL-2 must have normal heart, lung, liver and kidney function to be eligible. You will be evaluated to determine if you are an appropriate candidate for IL-2.

How it is given: It should be given in a hospital under the supervision of a qualified physician experienced in the use of IL-2. An intensive care facility and specialists skilled in cardiopulmonary or intensive care medicine must be available.

The drug is given via an IV line 3 times a day for 5 days (cycle 1), followed by 9 days of rest, followed by 5 days of treatment (cycle 2). This is considered one treatment course. You will typically get imaging done after the first treatment course and if you are responding, you will receive a second course of treatment and possibly a third course.

Effectiveness: IL-2 shrinks tumors in about 15% of patients. However, about 5% of patients get a complete response that can last 7 years or more.

Side effects: IL-2 can have very serious side effects, the most serious being a condition called “capillary leak” which occurs when fluids and proteins leak from the blood vessels, causing dangerously low blood pressure.

The most common side effects include:

  • nausea, vomiting, diarrhea, loss of appetite
  • weakness and fatigue
  • flu-like symptoms (fever, chills, headache and muscle aches)
  • low blood pressure
  • general pain, chest pain (angina)
  • breathing problems due to fluid in the lungs
  • weight gain, fluid retention
  • mental effects (paranoia, hallucinations, insomnia)
  • itching, peeling skin
  • anemia (low red blood cell count)
  • low platelet count (increasing the risk of bleeding)
  • low white blood cell count
  • kidney damage
  • mouth sores

Additional information/resources:

Reimbursement and Patient Assistance. Proleukin Patient Assistance Program 1-877-776-5385

Product Information: 1-877-378-4919

Proleukin Treatment Centers: https://secure.prometheuslabs.com/proleukin/mm/search-treatment-centers.aspx

SYLATRON (peginterferon alfa-2b)

Purpose: Sylatron is given to rev up the immune system in order to kill melanoma cells. Sylatron is given to prevent the cancer from coming back after the initial therapy, such as surgery.

How it works: Interferon is a naturally occurring protein that fights viral infections and other diseases. While the drug’s main function is to alert the immune system to kill the melanoma cells, its mechanism is not completely understood. It is possible that it also chokes the blood supply to the tumor (antiangiogenesis) and directly fights the tumor growth. Pegylation allows interferon to stay in the blood longer, so the drug can be given at a lower dose and for a longer period of time than high-dose interferon (Intron A).

Which patients: Sylatron is given to patients with microscopic or macroscopic nodal melanoma within 84 days of surgical resection that includes therapeutic lymph node dissection.

How it is given: Pegylated interferon is given subcutaneously at a higher dose for 8 doses followed by a lower dose (which can be given once a week) for up to 5 years. The dose is adjusted based on weight. Acetaminophen is given prior to the first dose and as needed thereafter.

Effectiveness: Sylatron is effective in delaying or preventing relapse of melanoma. The drug has not demonstrated a benefit on overall survival.

Side effects: Sylatron is better tolerated than Intron A. However, it still can cause acute flu-like symptoms within 4-8 hours of injection including fever, chills, muscle pain, headache, nausea, vomiting, fatigue, low white blood cell and red blood cell counts, liver damage, depression, loss of appetite, and impaired cognitive function (diminished attention/memory).

Additional information/resources:

Patient assistance: ACT program. 1-866-363-6379 http://www.merck.com/merckhelps/act-program/home.html

TAFINLAR (dabrafenib)

Purpose: Tafinlar blocks a cellular pathway to stop the growth of melanoma tumors.

How it works: Tafinlar is a kinase inhibitor that blocks the activity of the V600E-mutated form of BRAF, a key protein that helps cancer cells grow. About half of patients with melanoma have this mutated form of the protein in their tumors.

Which patients: Tafinlar is FDA-approved for adult patients who carry the BRAF V600E mutation and who have unresectable Stage III melanoma (melanoma that cannot be removed by surgery) or Stage IV melanoma. Before receiving Tafinlar, patients must test positive for the BRAF mutation.

How it is given: Tafinlar is an oral drug. Patients receive 150 mg orally twice daily.

Effectiveness: In a large clinical trial, progression-free survival (the time a patient lives without cancer growing or spreading) was 5.1 months for patients on Talfinar versus 2.7 months for patients on standard chemotherapy.

In the phase III clinical trial, comparing Tafinlar to dacarbazine (chemotherapy), 52% of all patients treated with Tafinlar experienced tumor shrinkage compared to 17% who received dacarbazine.

In a phase II clinical trial, Taflinar was evaluated in patients with the BRAF V600E mutation whose melanoma had spread to the brain. In this trial, 18% of the patients, both those who had local treatment for brain metastases and those who did not have local treatment for brain metastastes, showed a shrinkage in their brain metastases.

Side effects: Several side effects are common in the course of treatment. Most of these side effects are mild or moderate, although there have been some severe side effects. These side effects can usually be managed with either a decrease in the dosage or by briefly stopping the drug and then resuming its use after the symptoms improve. Sometimes, when the drug is resumed, it is at a lower dose.

  • New Skin Cancers
    • Cutaneous Squamous Cell Carcinoma (cuSCC), occurs in approximately 11% of patients. Of those who developed a cuSCC, approximately 33% went on to develop one or more additional cuSCC’s
    • New primary melanomas occur in approximately 2% of patients
    • If these lesions appear they should be removed, but typically you can continue taking the drug without changing the dosage

Important: You should have a dermatologic examination before you start Tafinlar, every two months while you remain on the drug, and up to 6 months after you stop taking the drug.

  • Serious Fevers: 28% of all patients developed fevers. In 3.7% of patients these fevers were serious and were accompanied by one or more of the following symptoms:
    • Low Blood Pressure
    • Chills
    • Dizziness
    • Too much fluid loss (dehydration)
    • Kidney problems

Important: Tell your doctor immediately if you get a fever.

  • Blood Sugar Problems (diabetes): Some people may develop high blood sugar or if they have diabetes it may get worse. Tell your doctor if you have any of the following symptoms:
    • Increased thirst
    • Urinating more than usual
    • Your breath smells like fruit
  • Eye problems such as uveitis occurred in 1% of patients. Symptoms include eye pain, swelling or redness, blurred vision or other vision changes

Important: You should have your eyes examined before and while you are taking Tafinlar. Tell your doctor immediately if any eye symptoms appear.

The most common side effects include:

  • Thickening of the outer layer of the skin
  • Headache
  • Joint pain
  • Warts
  • Hair loss
  • Redness, swelling, peeling, or tenderness of the hands or feet

Additional information/resources:

Patient assistance: Patients can call 1-8ONCOLOGY1 (1-866-265-6491)

YERVOY (ipilimumab)

Purpose: Yervoy is an anti-CTLA-4 monoclonal antibody. It is designed to restore and strengthen the immune system by supporting the activation and proliferation of T-cells, a critical component of the immune system. By supporting T-cells, Yervoy helps sustain an active immune response to fight the cancer cells.

How it works: Yervoy is a human monoclonal antibody designed to block the activity of a molecule called CTLA-4, a protein that normally helps keep the immune system cells, called T cells, in check. When Yervoy blocks CTLA-4, the drug “takes the breaks off the immune system” and allows T cells to activate and proliferate in order to attack the melanoma cells.

Which patients: Yervoy is approved for patients with unresectable Stage III melanoma (melanoma that cannot be completely removed surgically) or Stage IV melanoma.

How it is given: Yervoy is given intravenously, each dose given over a 90-minute period. Yervoy is usually given every 3 weeks for up to 4 doses. It is given in an outpatient clinic, and does not require hospitalization.

Effectiveness: In a large clinical trial, patients who were treated with Yervoy plus GP100, a peptide vaccine, showed a significant improvement in overall survival versus those who received GP100 alone. Higher estimated survival rates were observed at one year (46% vs. 25%) and at two years (24% vs.14%). Yervoy improved overall median survival by four months.

In a 2013 analysis of data collected from 12 prospective and retrospective studies of 1861 patients, it was shown that the median overall survival for patients treated with Yervoy was 11.4 months Among these patients, 22% were still alive after three years. There were no deaths among patients who survived beyond seven years, at which time the overall survival rate was 17%.

Side effects: Because Yervoy makes T cells more responsive to many stimuli (not just cancer cells), the drug can cause powerful autoimmune reactions in which the immune system attacks normal cells in the body. 15% of patients reported autoimmune reactions that were classified as severe and some fatalities did occur in the studies of Yervoy.

  • Colitis (inflammation of the colon), occurs in about 12% of patients. In 5% of the patients the symptoms are moderate, while in 7% of the patients the symptoms can be severe or life threatening, causing death in less than 1% of the cases. Signs and symptoms of colitis are:
    • diarrhea (loose stools) or more bowel movements than usual
    • blood in your stools or dark, tarry, sticky stools
    • stomach pain (abdominal pain) or tenderness

Important: If you develop diarrhea, you should call your doctor immediately. If you cannot reach your doctor go to the nearest emergency room. For the majority of patients, if found early, diarrhea can be controlled within a few days.

  • Hepatitis: An inflammation of the liver that occurs in less than 5%-10% of cases, but can lead to liver failure. Since it rarely has symptoms, it is important that your liver function be tested before you start Yervoy and during treatment, to identify any elevation in liver enzymes. Signs and symptoms of hepatitis may include:
    • yellowing of your skin or the whites of your eyes
    • dark urine (tea colored)
    • nausea or vomiting
    • pain on the right side of your stomach
    • bleeding or bruising more easily than normal

Important: Before each dose of Yervoy, your blood should be checked for liver function.

  • Skin/Toxicity/Rash: Occurs in about 50% of patients. Typically, it is a rash that comes and goes without itch. However, it can present as a more severe skin reaction (toxic epidermolysis necrolysis). Signs and symptoms of a severe skin reaction are:
    • skin rash with or without itching
    • sores in your mouth
    • skin blisters and/or peels
  • Inflammation of Hormone Glands: Dysfunction of the pituitary, adrenal, or thyroid glands, which occurs less than 10% of the time. Signs and symptoms that your glands are not working properly include:
    • persistent or unusual headaches
    • unusual sluggishness, feeling cold all the time, or weight gain
    • changes in mood or behavior such as decreased sex drive, irritability, or forgetfulness
    • dizziness or fainting

Important: The most common way inflammation of the hormone glands is determined is through blood work. Your physician should monitor this at regular intervals. If you have a preexisting thyroid problem before you start this medicine, it’s even more important to watch your blood counts and to make your physician aware of this so that this can be safely monitored.

Other Side Effects:

  • Inflammation of the Nerves: This can lead to paralysis. Symptoms of nerve problems may include:
    • unusual weakness of legs, arms, or face
    • numbness or tingling in hands or feet
  • Inflammation of the Eyes: Symptoms may include:
    • blurry vision, double vision, or other vision problems
    • eye pain or redness

Additional information/resources:

Financial Support: Click here
Y.E.S. Program: Click here
Risk Evaluation and Mitigation Strategy (REMS Program): Click here

ZELBORAF (vemurafenib)

Purpose: Zelboraf blocks a cellular pathway to stop the growth of melanoma tumors.

How it works: Zelboraf is a kinase inhibitor that blocks the activity of the V600E-mutated form of BRAF, a key protein that helps cancer cells grow. About half of patients with melanoma have this mutated form of the protein in their tumors.

Which patients: Zelboraf is FDA-approved for patients who carry the BRAF V600E mutation and who have unresectable Stage III melanoma (melanoma that cannot be removed surgically) or Stage IV melanoma. Before receiving Zelboraf, patients must test positive for the BRAF mutation.

How it is given: Zelboraf is an oral drug. Patients receive 960 mg orally twice daily.

Effectiveness: In a large clinical trial, comparing Zelboraf to DTIC, almost 50% of all patients treated with Zelboraf experienced tumor shrinkage compared to 5% who received DTIC. It is not yet clear how long Zelboraf can increase overall survival, but at the time the trial was studied 77% of the people taking Zelboraf were still alive, compared to 64% of those taking DTIC.

In the phase III clinical trial, progression-free survival (the time a patient lives without cancer growing or spreading) was 5.3 months for patients on Zelboraf versus 1.6 months for patients on standard chemotherapy.

Side effects: Several side effects are common early in the course of treatment. Most of these side effects are mild or moderate in severity and, when severe, can be managed with either a decrease in the dosage or by briefly stopping the drug and then resuming its use.

  • Cutaneous Squamous Cell Carcinoma, occurs in approximately 24% of patients and is by far the most common side effect.
    • These usually appear in the first 7 to 8 weeks of treatment.
    • Squamous cell carcinoma is seen most often in older patients, those with a history of skin cancer, and those who have experienced chronic sun exposure.
    • If these lesions appear they should be removed, but typically you can continue taking the drug without changing the dosage.

Important: You should have a dermatologic examination before you start Zelboraf and every two months while you are on the drug.

  • Severe Allergic Reaction May cause:
    • Blisters on the skin and blisters or sores in the mouth
    • Peeling of the skin
    • Fever
    • Swelling of the face, hands, or soles of the feet
  • Skin Rash is also very common. The rash usually appears on the arms and legs but can also appear on the chest and back.
    • It often appears over the course of several days and may cause itching.
    • This is usually a reversible side effect, and once the drug is temporarily stopped the rash generally improves very quickly, and often does not return when the medication is restarted.
    • In severe cases a patient may need to discontinue use of the drug.

Important: If the rash is uncomfortable and if it covers more than half of the body, you should call your doctor. The doctor will decide whether it is necessary to temporarily stop the therapy and also when to resume and at what dosage.

  • Increased Sensitivity to the Sun (photosensitivity) is also common. You should avoid going out in the sun as much as possible.

Important: When you do go outside, cover up with clothing that protects your skin, including head, face, hands, arms and lips. Use a sunscreen with an SPF of 30 or higher and use a lip balm.

  • Joint Discomfort is another relatively common side effect that usually occurs early in the course of treatment. Joint discomfort may involve one or multiple joints. The hands and feet are often painful, but the knees or shoulders can also be affected. On occasion swelling and redness around the joints will occur.

Important: Nonsteroidal antiinflammatories (aspirin-like medications) can be used to control the discomfort. In severe cases a dose interruption or reduction may be necessary.

Other Side Effects: These may include:

    • Changes in the electrical activity of the heart (QT prolongation) that can cause irregular heartbeats that are potentially life-threatening. Symptoms include feeling faint, lightheaded, dizzy or irregular or fast heartbeat.
    • Liver problems: symptoms include skin or the whites of the eyes turning yellow, feeling tired, dark or brown urine, nausea or vomiting, pain on the right side of the stomach
    • Eye problems such as uveitis. Symptoms include eye pain, swelling or redness, blurred vision or other vision changes
    • New primary malignant melanomas
    • Hair loss
    • Tiredness
    • Nausea
    • Warts

Additional information/resources:

Financial assistance. Zelboraf Access Solutions: 1-888-249-4918
Support: Patient Partners: 1-885-ZELBORAF (1-855-935-2672)

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