Capivasertib

Capivasertib (Truqap) is a targeted therapy used to treat hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancers that test positive for certain gene mutations. Capivasertib is the first FDA-approved breast cancer treatment that targets the AKT protein, which helps regulate cell growth, division, and survival.

Capivasertib is approved for use with the hormonal therapy fulvestrant (Faslodex). Fulvestrant works to stop hormone receptor-positive breast cancer cells from growing by slowing or stopping the activity of estrogen.

The FDA approval of capivasertib plus fulvestrant is based on the findings of the phase III CAPItello-291 clinical trial. This trial showed that in people with locally advanced or metastatic hormone receptor-positive breast cancer that tests positive for PIK3CA, AKT1, or PTEN mutations, capivasertib plus fulvestrant lowered the risk of progression or death when compared with fulvestrant alone. In people diagnosed with breast cancer that had AKT pathway mutations, the risk was lowered by 50%. In the overall study population, the risk was lowered by 40%.

How capivasertib works

AKT1, PIK3CA, and PTEN are proteins that all play a role within the PI3K-AKT pathway. Pathways within a cell are chains of molecules that pass messages, or signals, from one part of the cell to another. These signals tell the cell to do many things, such as grow, divide, or stop their activity.  

There are many pathways within a cell, and each pathway has its own role in a cell’s lifecycle. The PI3K-AKT pathway is a critical part of the process that allows tumor cells to grow and spread. Mutations in the PIK3CA, PTEN, or AKT genes are found in more than 35% of breast cancers and are more common in hormone receptor-positive breast cancers. 

The AKT protein sends signals to PIK3CA and PTEN proteins within the PI3K-AKT pathway. Capivasertib stops AKT from working. By blocking AKT’s processes, capivasertib ends AKT’s involvement in cell growth and spread and interrupts the activity of PI3K and PTEN in the pathway. 

Who gets capivasertib?

Capivasertib is available for people living with hormone receptor-positive, HER2-negative metastatic breast cancer that tests positive for an AKT1, PIK3CA, or PTEN mutation, after the breast cancer grows or spreads while on a hormonal therapy.

Capivasertib is also available to people who have a hormone receptor-positive, metastatic breast cancer diagnosis during or within 12 months of completing post-surgery (adjuvant) treatment with hormonal therapy for early-stage breast cancer. As with metastatic breast cancer, the tumor must test positive for an AKT1, PIK3CA, or PTEN mutation.

The CAPItello-291 trial showed that capivasertib plus fulvestrant improved outcomes for most participants with hormone receptor-positive metastatic breast cancer, even in breast cancer without genetic mutations. But the FDA ultimately approved the combination medicine only for people diagnosed with breast cancer that tests positive for AKT1, PIK3CA, and PTEN mutations because the improvement for people in this group was much stronger than for people diagnosed with breast cancer that did not have these mutations.

Tests to determine eligibility for capivasertib

Biomarker testing can determine whether you’re eligible to take capivasertib. If you haven’t had biomarker testing before, you’ll need to have a tissue sample tested before you can get capivasertib. Talk to your care team to find out if you have a tissue sample available from a past biopsy, or to schedule a biopsy for biomarker testing.

Getting capivasertib requires that the biomarker test be FDA approved to identify AKT1, PTEN, or PIK3CA mutations. Several tests exist that can detect mutations in these genes, but right now, the only FDA-approved test is FoundationOne CDx. Your doctor may use FoundationOne CDx or another test.

How capivasertib is given

Getting treatment with capivasertib plus fulvestrant includes taking capivasertib as a pill at home and going to your doctor’s office to get fulvestrant as an injection.

• Capivasertib is a 200 milligram (mg) pill. The recommended dose is two pills at a time, twice a day, 12 hours apart, so that the daily dose is 800 mg (400 mg in the morning and 400 mg in the evening). Each week, capivasertib is taken 4 days in a row, with a 3-day break before you take it again. Your doctor may recommend starting at a lower dose at first to monitor side effects. Talk with your doctor about the right dose for you.
• Fulvestrant is given as two 250 mg injections at the same time (for a total of 500 mg) at your doctor’s office. In the first month of treatment, you’ll get a fulvestrant injection on day 1 and day 15. After that, fulvestrant is given only once a month, on day one every 28 days.

You can take capivasertib with or without food, but be sure to avoid grapefruit or products that contain grapefruit or grapefruit juice. Grapefruit can change how well capivasertib works.

Side effects and things to remember

Here, you can learn about side effects and potential interactions with capivasertib, as well as recommendations to avoid pregnancy during and in the months after taking capivasertib.

Capivasertib side effects

The most common side effects of capivasertib are:

• Rash
• Diarrhea
• Increased blood sugar levels
• Low white blood cell counts
• Low red blood cell counts
• Nausea
• Fatigue
• High triglycerides, a type of lipid found in the blood
• Higher levels of creatinine, a waste product left after the body digests protein
• Vomiting
• Mouth sores

Rash and diarrhea were the most common reported side effects in the capivasertib plus fulvestrant group of the CAPItello-291 trial. Severe rash occurred in 12.1% of the treatment group, and diarrhea occurred in 9.3%. If you develop a rash or diarrhea, let your healthcare team know. They can make recommendations on how to manage these side effects. You can also learn more on LBBC’s Diarrhea and Nail and skin changes pages.

In the trial, changes in blood sugar levels were less common than diarrhea and rash. But blood sugar levels can have a significant impact on your health and how you feel.

Capivasertib caused higher-than-normal blood sugar in people both with and without diabetes, so your care team will check your blood sugar before and during treatment. If you develop high blood sugar, it may require treatment. Whether or not you have diabetes, let your doctors know if you experience:

• Extreme thirst
• Dry mouth
• Changes in the amount of urination
• Unexpected weight loss
• Fruity odor on your breath
• Dry or flushed (red) skin
• Blurred vision
• Fatigue

All of these can be signs of high blood sugar.

If you have diabetes, your doctors should monitor your sugar levels more often. Let them know if you see higher than normal sugar levels when doing your home tests. Right now, doctors don’t know if capivasertib is safe for people with Type I diabetes. If you’re living with diabetes, be sure to let your oncologist know, and talk with your oncologist and endocrinologist about using capivasertib. They should work together to track your lab test results and overall health.

Capivasertib drug and food interactions

Taking medicines called CYP3A inhibitors and CYP3A inducers may change the way capivasertib works. If you are taking a CYP3A inhibitor or inducer, your doctors will need to adjust the dose of capivasertib given to you, or, in some cases, you may need to change your medicines.

CYP3A inhibitors include:

• Erythromycin, a common antibiotic
• Ketoconazole, an antifungal medicine (the oral dose can interact with capivasertib; there is less risk with the topical dose)
• Clarithromycin, an antibiotic often used for skin and respiratory infections
• Verapamil, a medicine used to treat high blood pressure, chest pain, and some heart rhythm disorders

CYP3A inducers include:

• Glucocorticoids, a type of steroid used to treat inflammation
• Rifampin, a strong antibiotic used for infections such as tuberculosis and meningitis
• Carbamazepine, a medicine used to prevent seizures, and sometimes in the treatment of bipolar disorder
• Phenobarbital, a sedative used to prevent seizures
• Phenytoin, a medicine used to control seizures

Always share a list of medicines and supplements you take with your healthcare team. If you’re taking a CYP3A inhibitor or inducer, or if you aren’t sure, talk with your care team about this before starting treatment with capivasertib.

As mentioned above, avoid grapefruit and grapefruit juice while taking capivasertib, because it can change the way capivasertib works.

Capivasertib and pregnancy warnings

Capivasertib can harm an unborn baby. If you’re pregnant or think you may be pregnant, talk to your doctor before starting capivasertib. If you’re able to become pregnant, you will be asked to take a pregnancy test before treatment begins. Pregnancy should be avoided during treatment and for 1 month after treatment with capivasertib ends. If you can get a partner pregnant, you should take steps to avoid this for up to 4 months after treatment with capivasertib ends.

Paying for capivasertib

The maker of capivasertib, AstraZeneca, has a patient assistance program to help you pay for your treatments. They offer two programs: one to help people who already have health insurance to cover their copays and out-of-pocket costs, and one that provides AstraZeneca medicines for free to people who have certain needs. You can find out more about their programs and how to apply on their financial resources website, where you can also learn about private organizations that may be able to offer even more support.

Paying for treatment isn’t the only financial cost of breast cancer. Traveling to and from appointments, taking time off from work, and paying for childcare are just some of the other factors that play a role. Learn more about resources and support for covering the cost of breast cancer on our Financial matters pages.