Tenosynovial giant cell tumor (TGCT) is a group of rare tumors. They are usually benign (not cancer) and tend to occur in people between 25 to 50 years old. The tumors affect areas of the joints and may cause pain, swelling, and inflammation. There are two types of TGCTs. Giant cell tumors of the tendon sheath (GCTTS) are small tumors that grow in a specific area of the joint, like in your hands or feet. Pigmented villonodular synovitis (PVNS) are widespread (or diffuse) tumors that affect the entire joint. Usually, one joint is involved like the knee or hip. Surgery is the most common treatment to remove the tumors and the inflamed joint tissue. Even after treatment, tumors may come back, especially if they are the diffuse type.
Turalio (pexidartinib) is approved to treat certain adults with TGCT that is not likely to get better with surgery. It is typically taken twice a day by mouth.
How Does Turalio Work?
People with TGCT have too much of a protein called colony stimulating factor 1 (CSF1). When this protein connects with colony stimulating factor 1 receptors (CSF1R), inflammation and tumor growth happen. Turalio is a kinase inhibitor that blocks CSF1R. It keeps the CSF1 protein from connecting and working. This seems to reduce tumor growth and size in people with TGCTs. Turalio can also help improve the range of motion of the affected joint
How Do I Use Turalio?
Turalio is an oral capsule that is usually taken twice a day with a low-fat meal (about 11 to 14 grams of total fat). Avoid taking Turalio with a high-fat meal (about 55 to 65 grams of total fat). Taking Turalio with a high-fat meal will increase the amount of Turalio in your blood and may cause more serious side effects. Swallow the capsules whole. Do not open, break, or chew the capsules.
Read the Medication Guide and follow directions from your health care provider about the exact dose that you need to take.
If you vomit after taking your dose of Turalio or if you miss a dose, take the next dose at your usual time.
How Was Turalio Studied?
A clinical study called ENLIVEN was done to evaluate the effectiveness and safety of Turalio compared to placebo in 121 adults with advanced TGCT when surgery was not recommended. Most of the people in the study were female (59%). The average age was 44 years old, and the study included White people (88%), Asian people (3%), Black people (3%), Pacific Islander/Native Hawaiian people (3%), and Native Americans (2%). Most of the people had diffuse TGCT (88%) with disease involving the knee (61%), ankle (18%), hip (11%), wrist (3%), or foot (3%). Most people had surgery in the past (53%). People with cancer were not included in the study.
In the first part of the study, people were randomly selected to take either Turalio or a placebo for 24 weeks. The placebo looked like Turalio but did not contain any medicine. Neither the people in the study nor the doctors knew who received Turalio or who got the placebo.
People who completed part 1 were able to enter part 2 of the study where everyone knowingly took Turalio. If people had worsening disease before the end of part 1 and were taking the placebo, they were able to enter part 2 early. Treatment continued until the disease got worse or people had unmanageable side effects.
The main goal of the study was to look at the overall response of Turalio compared to placebo. Overall response included people who had a complete or partial response. Complete response meant the tumor disappeared and partial response meant the tumors were decreased by 30% or more. The study also looked at changes in range of motion, decreases in tumor volume, symptoms, and duration of response.
What Benefits Were Seen?
The overall response rate in people who took Turalio for 25 weeks was 39% compared to 0% in people who took the placebo. In 15% of people, the tumors disappeared completely. In 23% of people, tumors were reduced by 30% or more. No one in the placebo group had a decrease in tumor size. After part 2 of the study, the overall response rate in people who took Turalio was 61%. For most people who had a complete or partial response, their response lasted for about 6.9 months in part 1 and 24.9 months in part 2 of the study. People taking Turalio had improved range of motion compared to placebo at 25 weeks.
Your results may differ from what was seen in clinical studies.
What Can I Do to Manage Side Effects?
Turalio may cause serious liver problems that can be severe and lead to death. These include liver failure and vanishing bile duct syndrome (VBDS), a liver injury that can cause the loss of bile ducts in the liver. Keep all appointments with your health care provider and lab. You will need a blood test to check for liver problems before you start treatment, every week for the first eight weeks, every two weeks for the next month, and every three months after that. If you get liver problems during treatment, you may need to have blood tests more often, or you may be sent to a liver specialist (a hepatologist).
If you notice yellowing of your skin or whites of your eyes or dark urine, stop taking Turalio and call your health care provider right away. Other signs of liver problems include:
- Lack of or loss of appetite
- Pain or tenderness in your right upper stomach area (abdomen)
- Feeling very tired
- Nausea or vomiting
- Fever
- Rash or itching
Turalio may make you more sensitive to the sun and you may burn more easily. Avoid spending too much time in the sun. Use sunscreen and wear protective clothing to protect your skin if you are in the sunlight.
What Types of Drug Interactions Can Happen?
Turalio can cause liver problems. Other medicines that cause liver problems should be avoided because the risk may be increased. Ask your health care provider if you are taking a medicine that causes liver problems.
Some medicines and foods such as grapefruit or grapefruit juice may increase the amount of Turalio in your blood. This may increase your risk for side effects. Avoid grapefruit and grapefruit juice while you are taking Turalio. Your health care provider may need to decrease your dose of Turalio if you are taking a medicine that interacts.
Some medicines, such as the supplement St. John’s wort and proton pump inhibitors like omeprazole (Prilosec), may decrease the amount of Turalio in your blood and make it less effective. Your health care provider may need to change your medicines to avoid this type of drug interaction.
Turalio can interact with other medicines, such as hormonal contraceptives or birth control pills, making them less effective. Avoid the use of hormonal contraceptives with Turalio. You will need to use other birth control methods while you are taking Turalio and for at least 1 month after your final dose. Talk to your health care provider about birth control methods.
Always tell your health care provider about any prescription or over-the-counter (OTC) medicines, vitamins/minerals, herbal products, and other supplements you are using or have recently taken. This will help make sure your medicines are safe together.
Is There Any Cost Assistance Available?
There is a patient support program, Daiichi Sankyo Access Central, that may help you afford Turalio. Your health care provider will help you get started. For questions or more information, you can contact the drugmaker at 800-850-4306 or visit https://dsiaccesscentral.com/HCP/TURALIO.
Getting a Specialty Medicine: What to Expect
Your health care provider will prescribe Turalio. It is a specialty medicine, which is a high-cost medication that is taken for rare, complex, or chronic (long-term) diseases. It will require a different process than picking up a prescription at your local pharmacy. You will use a specialty pharmacy for getting this medicine. The specialty pharmacy will reach out to you to discuss the details about how to ship Turalio to your house.
Your insurance may require approval for using Turalio, also called prior authorization. The insurance company reviews the prescription from your health care provider to make sure it is covered and determines the process that needs to be followed.
You may also be able to work with a representative from the drugmaker that can help you through the process of insurance coverage and with details around the specialty pharmacy shipping the medicine.
