Your treatment handbook

Transcription

1 Your treatment handbook Inlyta is a prescription medicine used to treat advanced kidney cancer (advanced renal cell carcinoma or RCC) when one prior drug treatment for this disease has not worked or has stopped working.

2 Everyone has a this. A reason why they stay in the fight. For some, it s about family. For others, friends. Or their favorite pastime. Their passion for work. Then there are the simple, incredible moments that make up every day. This means different things to different people. But what many advanced kidney cancer (advanced renal cell carcinoma or RCC) patients have in common is that desire to keep fighting. With that determination, your doctor s support, and treatment with INLYTA, you now have the added confidence of this you re continuing your fight against advanced RCC. What You Will Find in This Handbook If you or someone you care about has been prescribed INLYTA, this handbook can help you learn about INLYTA and advanced RCC. Included in this handbook is the following information: 03 About INLYTA Get helpful information you need about INLYTA, such as how it helps to fight tumors, how you should take INLYTA, and what you should tell your doctor before starting treatment. 10 Important Safety Information Find out what you should tell your doctor before starting treatment and read about the risks and possible side effects of INLYTA. 13 Side Effect Tips Learn about tips that may help to manage certain side effects of INLYTA. 17 Access INLYTA Find information on how to get INLYTA, or how to get help paying for it. 19 Advanced Kidney Cancer Read about the most common type of kidney cancer (advanced renal cell carcinoma or RCC), including how it starts and spreads. 21 More You Can Do Healthy choices you can make and where to find more support when you need it. 2

3 About INLYTA (axitinib) tablets What is INLYTA? INLYTA (pronounced in-light-ah ) was approved by the US Food and Drug Administration (FDA) on January 27, Inlyta is a prescription medicine used to treat advanced kidney cancer (advanced renal cell carcinoma or RCC) when one prior drug treatment for this disease has not worked or has stopped working. 3

4 About INLYTA (axitinib) tablets How INLYTA helps fight tumors In your body are 3 receptors called vascular endothelial growth factor (VEGF) receptors. These receptors play a role in how tumors grow and spread. The medicine in INLYTA is thought to work by targeting all 3 VEGF receptors. Animal and laboratory tests suggest that INLYTA binds to these receptors to help keep 2 basic actions of cancer, proliferation and angiogenesis, in check. Proliferation occurs when a cell divides to make more cells. In most organs of the body, the cells making up that organ tend to be the same size and shape. Cancer cells often proliferate at a much higher rate than normal cells and may grow in abnormal sizes and shapes. Stages of proliferation Angiogenesis is the growth of new blood vessels. This occurs in healthy organs. But when it occurs in tumors, these blood vessels are abnormal and contribute to tumor growth. Angiogenesis Tumor New blood vessel Important Safety Information Women should not take INLYTA if they are pregnant, plan to become pregnant, are breastfeeding, or plan to breastfeed. Taking INLYTA during pregnancy can cause the death of an unborn baby or birth defects. Both men and women taking INLYTA should use effective birth control during treatment with INLYTA. Talk to your doctor about birth control methods, or if you are pregnant or plan to become pregnant. 4

5 About INLYTA (axitinib) tablets Efficacy of treatment INLYTA is a prescription medicine used to treat advanced kidney cancer (advanced renal cell carcinoma or RCC) when one prior drug treatment for this disease has not worked or has stopped working. This is often referred to as second-line treatment. Results from a head-to-head clinical trial In a trial, INLYTA extended median progression-free survival (PFS) for some advanced RCC patients compared with others taking Nexavar (sorafenib). Extended median PFS by 2 months compared to Nexavar In this study, those who were treated with INLYTA experienced a median PFS of 6.7 months compared with 4.7 months among patients who were taking Nexavar. That s a 43% increase in median PFS. One-third less risk of progression In this study, the overall risk of disease progression, such as tumor growth or spread, or death, was decreased by about one-third with INLYTA compared to Nexavar. INLYTA is not a cure. The data represent an average and not all patients may experience the same results. Definitions Progression-free survival (PFS): One measure of how a cancer treatment is working is what s known as progression-free survival or PFS. This term refers to the length of time, from the start of treatment, that patients remain alive and their disease does not worsen. Median: The median is a kind of average. Median PFS means that half of the patients in a study experienced longer PFS and half experienced shorter PFS. Second-line treatment: A therapy prescribed when your first drug treatment has not worked or has stopped working. Nexavar is a registered trademark of Bayer Pharmaceuticals Corporation. (Continued on next page.) Important Safety Information INLYTA may cause serious side effects, including high blood pressure (hypertension), a problem with blood clots in your veins or arteries (sometimes leading to death), bleeding (sometimes leading to death), heart failure (sometimes leading to death), a tear (perforation) in your stomach or intestinal wall (sometimes leading to death), thyroid gland problems, reversible posterior leukoencephalopathy syndrome (RPLS), increased protein in your urine, and change in liver function. 5

6 About INLYTA (axitinib) tablets Efficacy of treatment (Continued from previous page.) INLYTA is a prescription medicine used to treat advanced kidney cancer (advanced renal cell carcinoma or RCC) when one prior drug treatment for this disease has not worked or has stopped working. This is often referred to as second-line treatment. Results from a head-to-head clinical trial In a trial, INLYTA extended median progression-free survival (PFS) for some advanced RCC patients compared with others taking Nexavar (sorafenib). (See page 5.) Neither medicine showed an advantage in overall survival This study also measured the total time patients on each medicine remained alive after starting treatment. There was no significant difference in overall survival between the patients taking INLYTA and the patients taking Nexavar. More than twice as many INLYTA patients saw their tumors shrink (overall response rate) Twice as many patients on INLYTA saw their tumors shrink (70 of 361 patients taking INLYTA compared with 34 of 362 patients taking Nexavar). INLYTA is not a cure. The data represent an average and not all patients may experience the same results. Definitions Overall survival: This is another measure of how a cancer treatment is working. It is the length of time that patients remain alive after starting treatment. This number includes all causes of death (cancer, treatment side effects, and other causes). It also includes time spent on later treatments. Overall response rate: Another measure of how a cancer treatment is working is tumor shrinkage. This rate includes patients whose tumors shrank 30% or more and whose response lasted for at least 4 weeks. Doctors refer to tumor shrinkage as the overall tumor response rate. Second-line treatment: A therapy prescribed when your first drug treatment has not worked or has stopped working. Nexavar is a registered trademark of Bayer Pharmaceuticals Corporation. Important Safety Information The most common side effects of INLYTA include diarrhea (frequent or loose bowel movements); high blood pressure; tiredness or feeling weak; decreased appetite; nausea; hoarseness; rash, redness, itching or peeling of your skin on your hands or feet; decreased weight; vomiting; and constipation. Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of INLYTA. For more information, ask your doctor or pharmacist. 6

7 About INLYTA (axitinib) tablets INLYTA is available as a tablet and offers the ease of being taken by mouth. Before starting INLYTA, it s important to talk first with your doctor about any conditions you may have, as well as any medicines you might be taking. Before taking INLYTA Tell your doctor if you: - Have high blood pressure - Have thyroid problems - Have liver problems - Have a history of blood clots in your veins or arteries (types of blood vessels), including stroke, heart attack, or change in vision - Have any bleeding problems - Have a history of heart failure - Have an unhealed wound - Plan to have surgery. You should stop taking INLYTA at least 24 hours before planned surgery - Have any other medical conditions For females, tell your doctor if you: - Are pregnant or plan to become pregnant. Taking INLYTA during pregnancy can cause the death of an unborn baby or birth defects. You should not become pregnant while taking INLYTA. Talk to your doctor if you are pregnant or plan to become pregnant - Are able to become pregnant. You should use effective birth control during your treatment with INLYTA. Talk to your doctor about birth control methods to prevent pregnancy while you are taking INLYTA - Are breastfeeding or plan to breastfeed. It is not known if INLYTA passes into your breast milk. You and your doctor should decide if you will take INLYTA or breastfeed. You should not do both For males: - Use effective birth control during your treatment with INLYTA. Talk to your doctor about birth control methods - If your female partner becomes pregnant while you are taking INLYTA, tell your doctor right away 7

8 About INLYTA (axitinib) tablets Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. INLYTA and certain other medicines can affect each other causing serious side effects. Especially tell your doctor if you take: Dexamethasone Bosentan Modafinil St. John s wort (Hypericum perforatum) Medicine for: - Asthma - Seizures - Fungal infections - HIV/AIDS - Tuberculosis - Bacterial infections - Depression Ask your doctor or pharmacist if you are not sure if your medicine is one listed above. If you are taking any medicines for the conditions listed above, your doctor might need to prescribe a different medicine or your dose of INLYTA may need to be changed. Talk with your doctor before you start taking any new medicine. Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine. Grapefruit-Free Zone Do not drink grapefruit juice or eat grapefruit. Grapefruit may increase the amount of INLYTA in your blood. How to take INLYTA INLYTA comes in 1-mg and 5-mg tablets. Your doctor will tell you which tablets you should take. - Take INLYTA exactly as prescribed by your doctor - Your doctor may change your dose if needed - INLYTA can be taken with or without food - Take INLYTA 2 times a day approximately 12 hours apart - Swallow INLYTA tablets whole with a glass of water - Your doctor should check your blood pressure regularly during treatment with INLYTA - If you vomit or miss a dose of INLYTA, take your next dose at your regular time. Do not take 2 doses at the same time - If you take too much INLYTA, call your doctor or go to the nearest hospital emergency room right away 5 mg 1 mg 8

9 About INLYTA (axitinib) tablets Helpful reminders for taking each dose Make medicine a part of your daily routine. Take your medicine every day at the same times, 12 hours apart. For example, you may want to take it when you wake up in the morning and just after dinner Use a weekly or monthly pill caddy. It can help you keep count of your tablets in advance, and to remember to take each day s dosage Plan ahead. If possible, get your refills before your next treatment cycle starts Place your pill bottle in plain sight. Keep your medicine where you will see it, such as on your nightstand. Just make sure it is out of the reach of children and pets Always carry an extra dose with you. No matter where you are, you will always have your medicine on hand Use a calendar. Record your dosage times on a calendar or planner. You can then check off each dose as you take it Use a journal to track your medicine and when it is time to take it. You can also use it to track symptoms and side effects for doctor visits Ask for a reminder. A caregiver, friend, or family member can help remind you to take each dose of your medicine. Just ask Work with your healthcare team It s important to optimize the time you have with your healthcare team. Here are 3 tips to help you get organized and make the most of doctor visits: Use a journal to note your other medicines, questions, and experiences with your disease and treatment. That way, you can share them with your healthcare team. Speak your mind. Be sure your healthcare team knows when you have questions or want more information. Never be afraid to reach out and express yourself. Store direct office numbers and addresses for your healthcare team in one convenient place. Having this information handy will save you time when you have a question. 9

10 Important Safety Information Review important safety information prior to taking INLYTA When starting treatment with INLYTA, it s important that you review the safety information in this section. Inside, you will find information you should share with your doctor before taking INLYTA. You will also see a list of the risks and possible side effects associated with INLYTA. Make note of all your side effects and how you re feeling Be sure to pay attention to all your side effects. They can be important signs that let you and your doctor know what is happening in your body. Before starting INLYTA, tell your doctor how you are feeling and about any side effects you have had from other medicines and treatments. As you start taking INLYTA, let your doctor know if you notice any side effects or a change in how you feel. Also tell your doctor if you notice any side effects that are not listed in this brochure. Based on your experience, your doctor may change your dose or stop treatment with INLYTA. Please see full Prescribing Information and Patient Information, including a complete discussion of the risks of INLYTA, 10

11 Important Safety Information Important safety information Before you take INLYTA, tell your doctor if you: - Have high blood pressure - Have thyroid problems - Have liver problems - Have a history of blood clots in your veins or arteries (types of blood vessels), including stroke, heart attack, or change in vision Tell your doctor and pharmacist about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. INLYTA and certain other medicines can affect each other causing serious side effects. Talk with your doctor before you start taking any new medicine. Especially tell your doctor if you take dexamethasone, bosentan, modafinil, St. John s wort (Hypericum perforatum), or medicine for asthma, tuberculosis, seizures, bacterial infections, fungal infections, depression, or HIV/AIDS. Do not drink grapefruit juice or eat grapefruit. Pregnancy and breastfeeding. Women should not take INLYTA if they are pregnant, plan to become pregnant, are breastfeeding, or plan to breastfeed. Taking INLYTA during pregnancy can cause the death of an unborn baby or birth defects. Both men and women taking INLYTA should use effective birth control during treatment with INLYTA. Talk to your doctor about birth control methods, or if you are pregnant or plan to become pregnant. INLYTA may cause serious side effects, including: High blood pressure (hypertension). In a clinical study, hypertension occurred as early as 4 days into treatment. On average, this increase was seen within the first month of treatment. Your doctor should check your blood pressure regularly during treatment with INLYTA. If you develop blood pressure problems, your doctor may prescribe medicine to treat your high blood pressure, loweryour dose, or stop your treatment with INLYTA Problem with blood clots in your veins or arteries. Because this can be serious and sometimes lead to death, get emergency help and call your doctor if you get any of the following symptoms: - Chest pain or pressure - Pain in your arms, back, neck or jaw - Vision changes Bleeding. INLYTA can cause bleeding which can be serious, and sometimes lead to death. Call your doctor right away or get medical help if you develop any of the following signs or symptoms: - Unexpected bleeding or bleeding that lasts a long time, such as: - Unusual bleeding from the gums - Menstrual bleeding or vaginal bleeding that is heavier than normal - Bleeding that is severe or you cannot control - Pink or brown urine - Unexpected pain, swelling, or joint pain - Headaches, feeling dizzy or weak - Shortness of breath - Numbness or weakness on one side of your body - Have any bleeding problems - Have a history of heart failure - Have an unhealed wound - Plan to have surgery. You should stop taking INLYTA at least 24 hours before planned surgery - Have any other medical conditions - Trouble talking - Headache - Red or black stools (looks like tar) - Bruises that happen without a known cause or get larger - Cough up blood or blood clots - Vomit blood or your vomit looks like coffee grounds (Continued on next page.) Please see full Prescribing Information and Patient Information, including a complete discussion of the risks of INLYTA, 11

12 Important Safety Information (Continued from previous page.) Heart failure. Your doctor should check for signs or symptoms of heart failure regularly during treatment with INLYTA. Heart failure can be serious and can sometimes lead to death. Tell your doctor if you have any of the following symptoms during your treatment with INLYTA: - Tiredness - Swelling of your stomach area (abdomen), legs, or ankles Tear in your stomach or intestinal wall (perforation). Because this can be serious and sometimes lead to death, get medical help right away if you get the following symptoms: - Severe stomach (abdominal) pain or stomach pain that does not go away - Vomit blood - Red or black stools Thyroid gland problems. Your doctor should do blood tests to check your thyroid gland function before and during your treatment with INLYTA. Tell your doctor if you have any of the following symptoms during your treatment with INLYTA: - Tiredness that worsens or that does not go away - Weight gain or weight loss - Feeling hot or cold - Hair loss - Your voice deepens - Muscle cramps and aches Reversible Posterior Leukoencephalopathy Syndrome (RPLS). A condition called reversible posterior leukoencephalopathy syndrome (RPLS) can happen while taking INLYTA. Call your doctor right away if you get: - Headache - Confusion - Blindness or change in vision - Seizures - High blood pressure - Problems thinking - Weakness Increased protein in your urine. Your doctor should check your urine for protein before and during your treatment with INLYTA. If you develop protein in your urine, your doctor may decrease your dose of INLYTA or stop your treatment Change in liver function. Your doctor should do blood tests before and during your treatment with INLYTA to check your liver function The most common side effects of INLYTA include: - Diarrhea (frequent or loose bowel movements) - High blood pressure - Tiredness or feeling weak - Decreased appetite - Nausea - Hoarseness - Shortness of breath - Protruding neck veins - Rash, redness, itching or peeling of your skin on your hands or feet - Decreased weight - Vomiting - Constipation Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of INLYTA. For more information, ask your doctor or pharmacist. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call FDA Please see full Prescribing Information and Patient Information, including a complete discussion of the risks of INLYTA, 12

13 Side Effect Tips Ways to help manage certain common side effects The tips in this section are based on published general guidelines for managing side effects common among people with advanced RCC or other cancers. Not all side effects are manageable. Dose interruptions and/or reductions may be needed during treatment with INLYTA. Be sure to talk to your healthcare professional about any side effects you experience and how they may be managed for you. High blood pressure In a clinical study, hypertension occurred as early as 4 days into treatment. On average, this increase was seen within the first month of treatment. INLYTA may cause your blood pressure to rise. Your doctor should check your blood pressure regularly while you are being treated with INLYTA. If you develop blood pressure problems, your doctor may prescribe medicine to treat your high blood pressure, lower your dose, or stop your treatment with INLYTA. Tell your doctor or nurse if you have high blood pressure or a history of heart disease. If you have high blood pressure, your healthcare provider s recommendations may include: - Take antihypertensive medications as prescribed - Recognize signs of potentially dangerous high blood pressure (eg, severe headache, shortness of breath, nosebleeds) - Follow healthy lifestyle choices: regular exercise, weight control, moderate alcohol consumption, sodium restriction If you are already being treated for your high blood pressure, your doctor may change your blood pressure medicine when you start taking INLYTA. Your doctor may also ask you to track your blood pressure regularly. Follow the advice of your doctor or nurse talk to them if you have any questions or concerns. 13

14 Side Effect Tips Diarrhea Diarrhea is more loose or watery stools/bowel movements than usual. If you have these symptoms, call your doctor or nurse. It is important for you and your doctor to try to manage diarrhea as soon as it begins. If you experience diarrhea, your healthcare provider s recommendations may include: - Try yogurt containing probiotics - Drink fluids, such as water, diluted cranberry - Eat foods containing soluble fiber juice, broth, or decaffeinated tea or coffee - Eat small but frequent meals - Ask your doctor or nurse if you can be treated with over-the-counter medications Tiredness or feeling weak While you are taking INLYTA, you may feel tired or weak. Call your doctor or nurse if you have these symptoms. If tiredness or feeling weak is a recurring problem, your healthcare provider s recommendations may include: - Take short naps and breaks instead of long ones - Eat well and drink plenty of fluids - Take short walks or do light exercise if you feel up to it - Do things that are relaxing, such as listening to music or reading - Stay as active as possible - Try to maintain normal work and social schedules - Ask your doctor if there are over-the-counter or prescription medications that may help you manage your condition 14

15 Side Effect Tips Decreased appetite or weight During treatment, you may have less desire to eat. But maintaining good nutrition and a healthy weight are important to your overall health. Protein and calories are even more vital to someone with cancer. If you have decreased appetite, you can discuss the following diet ideas with your doctor: - Eat several small meals a day 5 or 6 isn t out of the question - When you are hungry, eat - Enjoy snacks and strive to make them nutritious. Find calories and protein in dried fruits, nuts, cheeses, and even milkshakes - For added protein and calories, it can be a good idea to add gravy, butter, or cheese to your favorite foods - Drink fluids between meals rather than filling up with them during meals - If you are too tired to cook, ask a friend or family member to make you something. You may be surprised how many people are willing to help you - If mouth pain causes you to eat less, consider avoiding spicy foods. Eat foods that are soft or use a straw for liquids - If taste changes cause you to eat less, try cold or frozen foods to minimize taste. Flavor foods with herbs, sugar, or sauces to maximize taste. And keep a clean and healthy mouth by brushing and flossing often - If an upset stomach causes you to eat less, avoid heavy meals, coffee, and alcohol; try sleeping in an upright position; and reduce stress with meditation, yoga, or music - A registered dietitian (RD) may have more ideas to offer you Ask your doctor if there are over-the-counter or prescription medicines that may help you manage your condition. Nausea or vomiting It is best to call your doctor or nurse at the first sign of nausea or vomiting. This is especially important if these symptoms keep you from taking your oral medications, or keeping them down. Your healthcare provider may prescribe a medicine for these symptoms. If you experience nausea or vomiting, your healthcare provider s recommendations may include: - Avoid fatty, fried, spicy, or highly sweet foods - Eat bland foods and drink clear liquids - Eat smaller, more frequent meals - Reduce food aromas and other stimuli with strong odors, and eat food at room temperature to lessen the odor - Listen to soft music, watch a favorite television program, or enjoy the company of others while you eat If you vomit, start with small amounts of water, broth, or other clear liquids when you are ready to eat again. If that stays down, then try soft foods. Some examples include gelatin, plain cornstarch pudding, yogurt, strained soup, or strained cooked cereal. Slowly work up to eating solid food. Make sure that you do not eat any food that you are allergic to. 15

16 Side Effect Tips Hoarseness Also called dysphonia (dis-phone-ee-uh), this is when you have a weak, rough, or harsh voice. If you have trouble speaking, your healthcare provider s recommendations may include: - Drink plenty of water and avoid irritants (eg, dust, smoke, alcohol, industrial chemicals) - Give your voice a break write things down - Avoid voice strain through shouting or whispering Skin conditions Skin conditions, such as rash, redness, or itching or peeling of skin, are other side effects you may have. You may notice dryness, thickening, calluses, or cracking of the skin on the palms of your hands and soles of your feet. This is called hand-foot syndrome. Some patients may have blisters or a rash. Tell your doctor or nurse if you start to develop skin problems. He or she may give you specific treatments, which may include lotions, moisturizers, or pain medicines. To help manage the effects of hand-foot syndrome, your healthcare provider s recommendations may include: - Wear loose cotton clothes - Apply creams containing lanolin or urea to - Use sunscreen the hands and feet liberally and often - Clean hands and feet with lukewarm water - Avoid tight-fitting shoes and jewelry or and gently pat dry rubbing pressure on the hands and feet - Do not shave off blisters Constipation Some people taking INLYTA experience constipation. This has the potential to become a serious side effect. Left untreated, constipation can cause a blockage in your intestines, leading to dehydration and even internal damage. If you experience constipation, speak to your doctor. He or she may recommend any of the following: - Drinking more fluids - Adding fiber to your diet - Taking a stool softener - Increasing physical activity - Changing your dose of INLYTA - Getting an enema 16

17 Access INLYTA (axitinib) tablets Learn about getting access to INLYTA INLYTA is available through Specialty Pharmacy Providers (SPP). These are pharmacies that handle medicines not often on hand at regular neighborhood pharmacies. If you need help determining which SPP to use, your doctor s office should be able to help you find one that s right for your insurance. You or your doctor s office can also call Pfizer RxPathways at One of its Patient Care Coordinators may be able to help you or your doctor s office identify an appropriate SPP. They will ask you a few basic questions, including your insurance information, before they identify an appropriate SPP. 17

18 Access INLYTA (axitinib) tablets Your co-pay could be covered. * If your prescription is covered by your insurance, but you need help with your co-pay, the INLYTA Co-Pay One Savings Card may be able to assist you. Insured patients who demonstrate significant financial hardship and meet income eligibility requirements can apply for the INLYTA Co-Pay One Savings Card. Many patients who qualify will receive help to cover the full cost of their co-pay. Visit to learn about the INLYTA Co-Pay One Savings Card, and see if you re eligible to start saving on your INLYTA prescriptions. * Limits, terms, and conditions apply. Co-pay program is also available to cash-paying patients. The maximum annual savings of $25,000 still applies. This offer is not health insurance. No membership fees. The offer will be accepted only at participating pharmacies. Please see the full terms and conditions online. Are you uninsured? Patients who are uninsured may be able to get their Pfizer medicine for free through the Pfizer RxPathways Patient Assistance Program. To be eligible, patients must: Have no prescription coverage Meet specific income guidelines, adjusted for family size Reside in the United States, US Virgin Islands, or Puerto Rico Be treated by a licensed physician in the United States or Puerto Rico If you need help right away or just want more information, please contact your Specialty Pharmacy Provider or visit INLYTA.com today. Proof of income is required to validate patient household income. Proof of income includes items such as the most recent federal income tax return, W-2 form(s), Social Security check, or a copy of the most recent pay stub. Proof of income is required within 30 days of enrollment. 18

19 RCC The Most Common Type of Kidney Cancer INLYTA is a prescription medicine used to treat advanced kidney cancer (advanced renal cell carcinoma or RCC) when one prior drug treatment for this disease has not worked or has stopped working. RCC is the most common type of kidney cancer. RCC starts in the kidney. It can start as one or more tumors in a single kidney. Less often, tumors form in both kidneys at the same time. How RCC starts and spreads Cancer cells are abnormal versions of healthy cells. They grow in many ways like these normal cells but do so at abnormal rates with irregular shapes. How these cells grow and spread: A single RCC cell grows and divides to form 2 cells. This process repeats, again and again A tumor can be detected once enough cancer cells are made Some cancer cells may enter the bloodstream, spreading from the kidney to other parts of the body New tumors may spread to other organs. If this happens, the cancer is known as metastatic. But no matter where the cancer spreads, it will still be called RCC, because it started in the kidney 19

20 RCC The Most Common Type of Kidney Cancer Stages of RCC There are 4 stages of RCC. To determine the cancer s stage, doctors will measure the tumor size. The images below are examples of different tumor sizes. Stage Stage I Stage II Stage III Stage IV Recurrent RCC Definition Tumor is found only in the kidney and is 7 centimeters or smaller. Tumor is found only in the kidney and is larger than 7 centimeters. Cancer may be found in the kidney, one nearby lymph node, an adrenal gland, the tissue around the kidney, or the main blood vessels of the kidneys. Cancer has spread beyond the kidney and may be found in multiple nearby lymph nodes or other organs, such as the intestines, pancreas, or lungs. Recurrent RCC is cancer that has returned after it has been treated, coming back in the kidney and/or in other parts of the body after the first treatment. Images are not actual size Golf ball (5 cm) Tennis ball (7 cm) 20

21 More You Can Do It may seem like there s the disease and the treatment and nothing else. But there are many things you can do to try and focus on what makes you happy and potentially feel better. There are also groups out there that offer support to people living with cancer. Help outside the doctor s office These healthy living tips are general information for anyone fighting cancer. Resting enough It s no secret that cancer and its treatment can wear you down. But for some, these changes can make it difficult to get rest. It s important to discuss changes in your sleep with your healthcare team. There are a few tips that may help you get rest if you are not sleeping enough. Taking a bath or shower, or listening to soothing music, before bedtime may help. Also, try taking short naps or breaks during the day. Staying active While cancer and its treatment can cause fatigue, it s still important to try and stay active. Ask your doctor before starting any activities. He or she may suggest simple ways to add exercise to your daily life. 21

22 More You Can Do Reducing stress Obviously, cancer takes a mental as well as physical toll. That can make it hard for you to simply be you. But if you think about the tips below, you may find a way to fight back, with old friends like food, relaxation, and more Try and relax: whether that means taking a deep breath, meditating, or praying, take moments for yourself - See if you are able to get more rest and exercise: review the tips on the previous page; they also happen to be good stress-busters - If you re comfortable, open up to people you trust: from friends and family members to therapists and religious leaders, sharing your feelings may ease the burden you carry - Eat what you love: just make sure to talk it over with your doctor so you don t adversely affect your health or treatment - Try to remember fun: watch comedies, spend time with friends, family and pets, and always try to keep the L-word in mind Laughter Staying informed If you re up for it, try and learn all you can about your type of cancer. Find reliable and credible resources for the latest, most current information about cancer and its treatment. Think about taking these steps: - First, talk openly with your healthcare team: track your symptoms and side effects. Alert your doctor about any changes, reactions, or side effects you may have - Be as organized as possible; log your activities and/or doctor appointments in a journal for easy reference, and include your insurance information Stop smoking If you are a current smoker, quitting now may improve your overall health. According to the National Cancer Institute: - Continuing to smoke may decrease the effectiveness of treatment and may worsen treatment side effects - If you have surgery for your cancer, continuing to smoke may cause your wounds to heal more slowly Talk to your doctor about quitting smoking. Eat right It s important to maintain a healthy weight and eat a well-balanced diet that includes more fruits, fresh vegetables, whole grains, and high-fiber foods. - Many people with cancer don t take in enough protein and calories. Getting a healthy balance of each can give you a better chance of healing well, fighting off infection, and maintaining your energy level - Along with protein, a healthy diet also includes nutrients, vitamins, minerals, carbohydrates, water, and fat. All can help to better support the body - Good nutrition and a healthy diet may help you to better manage the symptoms and side effects of cancer and its treatment 22

23 More You Can Do More resources and support for you In addition to allowing friends and loved ones to offer their help, think about this: living with cancer can cause you to have a wide range of emotions, including depression. Talking to others who live with cancer may help you cope with the challenges and changes that it can bring. The following list of organizations and resources are provided to help you learn more about cancer and where to tap into patient support services. The American Cancer Society (ACS) (800) cancer.org Get helpful advice and up-to-date news about treatment options and clinical studies, as well as inspirational stories from cancer survivors. National Cancer Institute (NCI) (800) cancer.gov This helpful resource offers facts and information about cancer, treatments, and clinical trials. It also provides advice on how to pay for treatment, as well as choosing hospice and home care, and how to find support groups. CancerCare (800) 813-HOPE ( ) cancercare.org Get helpful advice and counseling about cancer, such as disease information and free financial services. Cancer Hope Network (877) HOPENET ( ) cancerhopenetwork.org Support services for people living with cancer, which include matching patients one-on-one with cancer survivors. Kidney Cancer Association (KCA) (800) kidneycancer.org A dedicated group of patients, families, doctors, and healthcare providers involved with kidney cancer and its treatment. Learn simple ways to make living with kidney cancer easier, and how to find and connect with other patients and survivors. These organizations and resources are neither owned nor controlled by Pfizer. Pfizer is not responsible for their content or services. Keep This in Mind Get INLYTA INLYTA is available through a specialty pharmacy. If you are having trouble getting or paying for INLYTA, talk to your doctor or call Pfizer RxPathways at Work with your healthcare team Pay attention to how you re feeling as you take INLYTA. If you have side effects, your doctor or nurse may have ideas to help you manage them. Use this handbook as a guide The information and tips in this brochure may help you as you start out with INLYTA. Keep it with you. If you have questions, ask your healthcare team for more information. For more information, please visit INLYTA.com. 23

24 This Is About More Than Cancer Visit INLYTA.com today. And be sure to check back for the most up-to-date information about INLYTA and advanced renal cell carcinoma (RCC). Inlyta is a prescription medicine used to treat advanced kidney cancer (advanced renal cell carcinoma or RCC) when one prior drug treatment for this disease has not worked or has stopped working. AXU Pfizer Inc. All rights reserved. November 2014

25 HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use INLYTA safely and effectively. See full prescribing information for INLYTA. INLYTA (axitinib) tablets for oral administration Initial U.S. Approval: RECENT MAJOR CHANGES Warnings and Precautions, Cardiac Failure (5.5) 08/ INDICATIONS AND USAGE INLYTA is a kinase inhibitor indicated for the treatment of advanced renal cell carcinoma after failure of one prior systemic therapy. (1) DOSAGE AND ADMINISTRATION The starting dose is 5 mg orally twice daily. Dose adjustments can be made based on individual safety and tolerability. (2.1, 2.2) Administer INLYTA dose approximately 12 hours apart with or without food. (2.1) INLYTA should be swallowed whole with a glass of water. (2.1) If a strong CYP3A4/5 inhibitor is required, decrease the INLYTA dose by approximately half. (2.2) For patients with moderate hepatic impairment, decrease the starting dose by approximately half. (2.2) DOSAGE FORMS AND STRENGTHS mg and 5 mg tablets (3) CONTRAINDICATIONS None (4) WARNINGS AND PRECAUTIONS Hypertension including hypertensive crisis has been observed. Blood pressure should be well-controlled prior to initiating INLYTA. Monitor for hypertension and treat as needed. For persistent hypertension despite use of anti-hypertensive medications, reduce the INLYTA dose. (5.1) Arterial and venous thrombotic events have been observed and can be fatal. Use with caution in patients who are at increased risk for these events. (5.2, 5.3) Hemorrhagic events, including fatal events, have been reported. INLYTA has not been studied in patients with evidence of untreated brain metastasis or recent active gastrointestinal bleeding and should not be used in those patients. (5.4) FULL PRESCRIBING INFORMATION: CONTENTS* 1 INDICATIONS AND USAGE 2 DOSAGE AND ADMINISTRATION 2.1 Recommended Dosing 2.2 Dose Modification Guidelines 3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS 5 WARNINGS AND PRECAUTIONS 5.1 Hypertension and Hypertensive Crisis 5.2 Arterial Thromboembolic Events 5.3 Venous Thromboembolic Events 5.4 Hemorrhage 5.5 Cardiac Failure 5.6 Gastrointestinal Perforation and Fistula Formation 5.7 Thyroid Dysfunction 5.8 Wound Healing Complications 5.9 Reversible Posterior Leukoencephalopathy Syndrome 5.10 Proteinuria 5.11 Elevation of Liver Enzymes 5.12 Hepatic Impairment 5.13 Pregnancy 6 ADVERSE REACTIONS 6.1 Clinical Trials Experience 7 DRUG INTERACTIONS 7.1 CYP3A4/5 Inhibitors 7.2 CYP3A4/5 Inducers 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE INLYTA is indicated for the treatment of advanced renal cell carcinoma (RCC) after failure of one prior systemic therapy. 2 DOSAGE AND ADMINISTRATION 2.1 Recommended Dosing The recommended starting oral dose of INLYTA is 5 mg twice daily. Administer INLYTA doses approximately 12 hours apart with or without food [see Clinical Pharmacology (12.3)]. INLYTA should be swallowed whole with a glass of water. If the patient vomits or misses a dose, an additional dose should not be taken. The next prescribed dose should be taken at the usual time. 2.2 Dose Modification Guidelines Dose increase or reduction is recommended based on individual safety and tolerability. Over the course of treatment, patients who tolerate INLYTA for at least two consecutive weeks with no adverse reactions >Grade 2 (according to the Common Toxicity Criteria for Adverse Events [CTCAE]), are normotensive, and are not receiving anti-hypertension medication, may have their dose increased. When a dose increase from 5 mg twice daily is recommended, the INLYTA dose may be increased to 7 mg twice daily, and further to 10 mg twice daily using the same criteria. Over the course of treatment, management of some adverse drug reactions may require temporary interruption or permanent discontinuation and/or dose reduction of INLYTA therapy [see Warnings and Precautions (5)]. If dose reduction from 5 mg twice Cardiac failure has been observed and can be fatal. Monitor for signs or symptoms of cardiac failure throughout treatment with INLYTA. (5.5) Gastrointestinal perforation and fistula, including death, have occurred. Use with caution in patients at risk for gastrointestinal perforation or fistula. (5.6) Hypothyroidism requiring thyroid hormone replacement has been reported. Monitor thyroid function before initiation of, and periodically throughout, treatment with INLYTA. (5.7) Stop INLYTA at least 24 hours prior to scheduled surgery. (5.8) Reversible Posterior Leukoencephalopathy Syndrome (RPLS) has been observed. Permanently discontinue INLYTA if signs or symptoms of RPLS occur. (5.9) Monitor for proteinuria before initiation of, and periodically throughout, treatment with INLYTA. For moderate to severe proteinuria, reduce the dose or temporarily interrupt treatment with INLYTA. (5.10) Liver enzyme elevation has been observed during treatment with INLYTA. Monitor ALT, AST and bilirubin before initiation of, and periodically throughout, treatment with INLYTA. (5.11) The starting dose of INLYTA should be decreased if used in patients with moderate hepatic impairment. INLYTA has not been studied in patients with severe hepatic impairment. (2.2, 5.12) INLYTA can cause fetal harm when administered to a pregnant woman based on its mechanism of action. Women of childbearing potential should be advised of the potential hazard to the fetus and to avoid becoming pregnant while receiving INLYTA. (5.13, 8.1) ADVERSE REACTIONS The most common ( 20%) adverse reactions are diarrhea, hypertension, fatigue, decreased appetite, nausea, dysphonia, palmar-plantar erythrodysesthesia (hand-foot) syndrome, weight decreased, vomiting, asthenia, and constipation. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer, Inc at or FDA at FDA-1088 or DRUG INTERACTIONS Avoid strong CYP3A4/5 inhibitors. If unavoidable, reduce the INLYTA dose. (2.2, 7.1) Avoid strong CYP3A4/5 inducers. (7.2) See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling Revised: 8/ Nursing Mothers 8.4 Pediatric Use 8.5 Geriatric Use 8.6 Hepatic Impairment 8.7 Renal Impairment 10 OVERDOSAGE 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 12.2 Pharmacodynamics 12.3 Pharmacokinetics 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 14 CLINICAL STUDIES 16 HOW SUPPLIED/STORAGE AND HANDLING 17 PATIENT COUNSELING INFORMATION 17.1 Hypertension 17.2 Arterial/Venous Thromboembolic Events 17.3 Hemorrhage 17.4 Cardiac Failure 17.5 Gastrointestinal Disorders 17.6 Abnormal Thyroid Function 17.7 Wound Healing Complications 17.8 Reversible Posterior Leukoencephalopathy Syndrome 17.9 Pregnancy Concomitant Medications *Sections or subsections omitted from the Full Prescribing Information are not listed. daily is required, the recommended dose is 3 mg twice daily. If additional dose reduction is required, the recommended dose is 2 mg twice daily. Strong CYP3A4/5 Inhibitors: The concomitant use of strong CYP3A4/5 inhibitors should be avoided (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole). Selection of an alternate concomitant medication with no or minimal CYP3A4/5 inhibition potential is recommended. Although INLYTA dose adjustment has not been studied in patients receiving strong CYP3A4/5 inhibitors, if a strong CYP3A4/5 inhibitor must be co-administered, a dose decrease of INLYTA by approximately half is recommended, as this dose reduction is predicted to adjust the axitinib area under the plasma concentration vs time curve (AUC) to the range observed without inhibitors. The subsequent doses can be increased or decreased based on individual safety and tolerability. If co-administration of the strong inhibitor is discontinued, the INLYTA dose should be returned (after 3 5 half-lives of the inhibitor) to that used prior to initiation of the strong CYP3A4/5 inhibitor [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)]. Hepatic Impairment: No starting dose adjustment is required when administering INLYTA to patients with mild hepatic impairment (Child-Pugh class A). Based on the pharmaco kinetic data, the INLYTA starting dose should be reduced by approximately half in patients with baseline moderate hepatic impairment (Child-Pugh class B). The subsequent doses can be increased or decreased based on individual safety and tolerability. INLYTA has not been studied in patients with severe hepatic impairment (Child-Pugh class C) [see Warnings and Precautions (5.12), Use in Specific Populations (8.6), and Clinical Pharmacology (12.3)].

26 3 DOSAGE FORMS AND STRENGTHS 1 mg tablets of INLYTA: red, film-coated, oval tablets, debossed with Pfizer on one side and 1 XNB on the other side. 5 mg tablets of INLYTA: red, film-coated, triangular tablets, debossed with Pfizer on one side and 5 XNB on the other side. 4 CONTRAINDICATIONS None 5 WARNINGS AND PRECAUTIONS 5.1 Hypertension and Hypertensive Crisis In a controlled clinical study with INLYTA for the treatment of patients with RCC, hyper - tension was reported in 145/359 patients (40%) receiving INLYTA and 103/355 patients (29%) receiving sorafenib. Grade 3/4 hypertension was observed in 56/359 patients (16%) receiving INLYTA and 39/355 patients (11%) receiving sorafenib. Hypertensive crisis was reported in 2/359 patients (<1%) receiving INLYTA and none of the patients receiving sorafenib. The median onset time for hypertension (systolic blood pressure >150 mmhg or diastolic blood pressure >100 mmhg) was within the first month of the start of INLYTA treatment and blood pressure increases have been observed as early as 4 days after starting INLYTA. Hypertension was managed with standard antihypertensive therapy. Discontinuation of INLYTA treatment due to hypertension occurred in 1/359 patients (<1%) receiving INLYTA and none of the patients receiving sorafenib [see Adverse Reactions (6.1)]. Blood pressure should be well-controlled prior to initiating INLYTA. Patients should be monitored for hypertension and treated as needed with standard anti-hypertensive therapy. In the case of persistent hypertension despite use of anti-hypertensive medications, reduce the INLYTA dose. Discontinue INLYTA if hypertension is severe and persistent despite anti-hypertensive therapy and dose reduction of INLYTA, and discontinuation should be considered if there is evidence of hypertensive crisis. If INLYTA is interrupted, patients receiving antihypertensive medications should be monitored for hypotension [see Dosage and Administration (2.2)]. 5.2 Arterial Thromboembolic Events In clinical trials, arterial thromboembolic events have been reported, including deaths. In a controlled clinical study with INLYTA for the treatment of patients with RCC, Grade 3/4 arterial thromboembolic events were reported in 4/359 patients (1%) receiving INLYTA and 4/355 patients (1%) receiving sorafenib. Fatal cerebrovascular accident was reported in 1/359 patients (<1%) receiving INLYTA and none of the patients receiving sorafenib [see Adverse Reactions (6.1)]. In clinical trials with INLYTA, arterial thromboembolic events (including transient ischemic attack, cerebrovascular accident, myocardial infarction, and retinal artery occlusion) were reported in 17/715 patients (2%), with two deaths secondary to cerebrovascular accident. Use INLYTA with caution in patients who are at risk for, or who have a history of, these events. INLYTA has not been studied in patients who had an arterial thromboembolic event within the previous 12 months. 5.3 Venous Thromboembolic Events In clinical trials, venous thromboembolic events have been reported, including deaths. In a controlled clinical study with INLYTA for the treatment of patients with RCC, venous thromboembolic events were reported in 11/359 patients (3%) receiving INLYTA and 2/355 patients (1%) receiving sorafenib. Grade 3/4 venous thromboembolic events were reported in 9/359 patients (3%) receiving INLYTA (including pulmonary embolism, deep vein thrombosis, retinal vein occlusion and retinal vein thrombosis) and 2/355 patients (1%) receiving sorafenib. Fatal pulmonary embolism was reported in 1/359 patients (<1%) receiving INLYTA and none of the patients receiving sorafenib. In clinical trials with INLYTA, venous thromboembolic events were reported in 22/715 patients (3%), with two deaths secondary to pulmonary embolism. Use INLYTA with caution in patients who are at risk for, or who have a history of, these events. INLYTA has not been studied in patients who had a venous thromboembolic event within the previous 6 months. 5.4 Hemorrhage In a controlled clinical study with INLYTA for the treatment of patients with RCC, hemorrhagic events were reported in 58/359 patients (16%) receiving INLYTA and 64/355 patients (18%) receiving sorafenib. Grade 3/4 hemorrhagic events were reported in 5/359 (1%) patients receiving INLYTA (including cerebral hemorrhage, hematuria, hemoptysis, lower gastrointestinal hemorrhage, and melena) and 11/355 (3%) patients receiving sorafenib. Fatal hemorrhage was reported in 1/359 patients (<1%) receiving INLYTA (gastric hemorrhage) and 3/355 patients (1%) receiving sorafenib. INLYTA has not been studied in patients who have evidence of untreated brain metastasis or recent active gastrointestinal bleeding and should not be used in those patients. If any bleeding requires medical intervention, temporarily interrupt the INLYTA dose. 5.5 Cardiac Failure In a controlled clinical study with INLYTA for the treatment of patients with RCC, cardiac failure was reported in 6/359 patients (2%) receiving INLYTA and 3/355 patients (1%) receiving sorafenib. Grade 3/4 cardiac failure was observed in 2/359 patients (1%) receiving INLYTA and 1/355 patients (<1%) receiving sorafenib. Fatal cardiac failure was reported in 2/359 patients (1%) receiving INLYTA and 1/355 patients (<1%) receiving sorafenib. Monitor for signs or symptoms of cardiac failure throughout treatment with INLYTA. Management of cardiac failure may require permanent discontinuation of INLYTA. 5.6 Gastrointestinal Perforation and Fistula Formation In a controlled clinical study with INLYTA for the treatment of patients with RCC, gastro intestinal perforation was reported in 1/359 patients (<1%) receiving INLYTA and none of the patients receiving sorafenib. In clinical trials with INLYTA, gastrointestinal perforation was reported in 5/715 patients (1%), including one death. In addition to cases of gastro intestinal perforation, fistulas were reported in 4/715 patients (1%). Monitor for symptoms of gastrointestinal perforation or fistula periodically throughout treatment with INLYTA. 5.7 Thyroid Dysfunction In a controlled clinical study with INLYTA for the treatment of patients with RCC, hypo thyroidism was reported in 69/359 patients (19%) receiving INLYTA and 29/355 patients (8%) receiving sorafenib. Hyperthyroidism was reported in 4/359 patients (1%) receiving INLYTA and 4/355 patients (1%) receiving sorafenib. In patients who had thyroid stimulating hormone (TSH) <5 µu/ml before treatment, elevations of TSH to 10 µu/ml occurred in 79/245 patients (32%) receiving INLYTA and 25/232 patients (11%) receiving sorafenib [see Adverse Reactions (6.1)]. Monitor thyroid function before initiation of, and periodically throughout, treatment with INLYTA. Treat hypothyroidism and hyperthyroidism according to standard medical practice to maintain euthyroid state. 5.8 Wound Healing Complications No formal studies of the effect of INLYTA on wound healing have been conducted. Stop treatment with INLYTA at least 24 hours prior to scheduled surgery. The decision to resume INLYTA therapy after surgery should be based on clinical judgment of adequate wound healing. 5.9 Reversible Posterior Leukoencephalopathy Syndrome In a controlled clinical study with INLYTA for the treatment of patients with RCC, reversible posterior leukoencephalopathy syndrome (RPLS) was reported in 1/359 patients (<1%) receiving INLYTA and none of the patients receiving sorafenib [see Adverse Reactions (6.1)]. There were two additional reports of RPLS in other clinical trials with INLYTA. RPLS is a neurological disorder which can present with headache, seizure, lethargy, confusion, blindness and other visual and neurologic disturbances. Mild to severe hypertension may be present. Magnetic resonance imaging is necessary to confirm the diagnosis of RPLS. Discontinue INLYTA in patients developing RPLS. The safety of reinitiating INLYTA therapy in patients previously experiencing RPLS is not known Proteinuria In a controlled clinical study with INLYTA for the treatment of patients with RCC, proteinuria was reported in 39/359 patients (11%) receiving INLYTA and 26/355 patients (7%) receiving sorafenib. Grade 3 proteinuria was reported in 11/359 patients (3%) receiving INLYTA and 6/355 patients (2%) receiving sorafenib [see Adverse Reactions (6.1)]. Monitoring for proteinuria before initiation of, and periodically throughout, treatment with INLYTA is recommended. For patients who develop moderate to severe proteinuria, reduce the dose or temporarily interrupt INLYTA treatment Elevation of Liver Enzymes In a controlled clinical study with INLYTA for the treatment of patients with RCC, alanine aminotransferase (ALT) elevations of all grades occurred in 22% of patients on both arms, with Grade 3/4 events in <1% of patients on the INLYTA arm and 2% of patients on the sorafenib arm. Monitor ALT, aspartate aminotransferase (AST) and bilirubin before initiation of and periodically throughout treatment with INLYTA Hepatic Impairment The systemic exposure to axitinib was higher in subjects with moderate hepatic impairment (Child-Pugh class B) compared to subjects with normal hepatic function. A dose decrease is recommended when administering INLYTA to patients with moderate hepatic impairment (Child-Pugh class B). INLYTA has not been studied in patients with severe hepatic impairment (Child-Pugh class C) [see Dosage and Administration (2.2), Use in Specific Populations (8.6), and Clinical Pharmacology (12.3)] Pregnancy INLYTA can cause fetal harm when administered to a pregnant woman based on its mechanism of action. There are no adequate and well-controlled studies in pregnant women using INLYTA. In developmental toxicity studies in mice, axitinib was teratogenic, embryotoxic and fetotoxic at maternal exposures that were lower than human exposures at the recommended clinical dose. Women of childbearing potential should be advised to avoid becoming pregnant while receiving INLYTA. If this drug is used during pregnancy, or if a patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus [see Use in Specific Populations (8.1)]. 6 ADVERSE REACTIONS Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety of INLYTA has been evaluated in 715 patients in monotherapy studies, which included 537 patients with advanced RCC. The data described [see Adverse Reactions (6.1)] reflect exposure to INLYTA in 359 patients with advanced RCC who participated in a randomized clinical study versus sorafenib [see Clinical Studies (14)]. The following risks, including appropriate action to be taken, are discussed in greater detail in other sections of the label [see Warnings and Precautions ( )]: hypertension, arterial thromboembolic events, venous thromboembolic events, hemorrhage, cardiac failure, gastrointestinal perforation and fistula formation, thyroid dysfunction, wound healing complications, RPLS, proteinuria, elevation of liver enzymes, hepatic impairment and fetal development. 6.1 Clinical Trials Experience The median duration of treatment was 6.4 months (range 0.03 to 22.0) for patients who received INLYTA and 5.0 months (range 0.03 to 20.1) for patients who received sorafenib. Dose modifications or temporary delay of treatment due to an adverse reaction occurred in 199/359 patients (55%) receiving INLYTA and 220/355 patients (62%) receiving sorafenib. Permanent discontinuation due to an adverse reaction occurred in 34/359 patients (9%) receiving INLYTA and 46/355 patients (13%) receiving sorafenib. The most common ( 20%) adverse reactions observed following treatment with INLYTA were diarrhea, hypertension, fatigue, decreased appetite, nausea, dysphonia, palmar-plantar erythrodysesthesia (hand-foot) syndrome, weight decreased, vomiting, asthenia, and constipation. Table 1 presents adverse reactions reported in 10% patients who received INLYTA or sorafenib.