A study of alpelisib and hormone therapy for advanced breast cancer (BYLieve)

Please note - this trial is no longer recruiting patients. We hope to add results when they are available.

Cancer type:

Breast cancer
Secondary cancers




Phase 2

This study is looking at alpelisib with either fulvestrant or letrozole for advanced breast cancer that has continued to grow.

It is for men and women whose breast cancer has spread into surrounding tissue (is locally advanced) or elsewhere in the body. And whose breast cancer cells have:

  • receptors for oestrogen or progesterone (is hormone receptor positive)
  • low or no amounts of HER2 (this is called HER2 negative breast cancer)
  • a change to the PIK3CA gene

More about this trial

Hormone therapy is one of the usual treatments for advanced breast cancer. You might have this alongside a targeted cancer drug for example, palbociclib or ribociclib. They are both types of drugs CDK 4/6 inhibitors. Unfortunately for some people their cancer may not respond to this treatment or may come back afterwards. Doctors are looking for ways to treat these people.

In this study, they are looking at a drug called alpelisib (also known as BYL719). It is also a type of targeted cancer drug. It is called a cancer growth blocker. It works by blocking the actions of proteins called PI3K (a PI3K inhibitor). This can stop signals that cancer cells use to divide and grow.

Researchers think having alpelisib with the usual hormone therapy drugs fulvestrant or letrozole will help control the cancer. But they want to find out more.

The aims of the study are to:

  • find out how well treatment works
  • find out how safe it is
  • learn more about the side effects

Who can enter

The following bullet points list the entry conditions for this study. Talk to your doctor or the study team if you are unsure about any of these. They will be able to advise you.

Who can take part
You may be able to join this study if all of the following apply.

  • have breast cancer that has grown into surrounding tissues or spread elsewhere in the body
  • have breast cancer that has got worse during or after treatment with drugs called CDK 4/6 inhibitors such as palbociclib or ribociclib and this was the last treatment you had
  • have changes to the PIK3CA gene in your breast cancer cells
  • have cancer that has few, or no receptors for HER2 (it is HER2 negative)
  • have cancer that is hormone receptor positive (there are a large number of oestrogen or progesterone hormone receptors)
  • have 1 area of cancer that can be seen on a scan or the cancer has caused holes in the bone (lytic bone lesions) and you have at least 1 lesion
  • have satisfactory blood test results
  • are well enough to be up and about for at least half the day (performance status 0,1 or 2)
  • are willing to use reliable contraception for up to 8 months if you are a man and there is any chance your partner could become pregnant
  • are at least 18 years old

Who can’t take part
You cannot join this study if any of these apply.

Cancer related

  • have had treatment with the study drug (alpelisib) or a similar drug in the past
  • have had more than 2 different treatments for advanced breast cancer
  • have cancer that has spread to the brain or spinal cord or if you do, your treatment finished at least 28 days ago, it is stable and you haven’t taken steroids or drugs to control seizures in the last 2 weeks
  • have had tamoxifen for 14 days or longer or letrozole, anastrozole or goserelin for 28 days or longer
  • have cancer spread to the lymphatic system in the lungs
  • have had another cancer in the last 3 years apart from basal cell skin cancer, squamous cell skin cancer or cancer of the cervix that was successfully treated with surgery
  • have had radiotherapy in the last 4 weeks or radiotherapy for symptoms in the last 2 weeks before you join the trial and you have side effects unless they are mild apart from hair loss
  • are having or have had steroid treatment in the 2 weeks before starting alpelisib or you still have side effects from this treatment
  • have had an experimental treatment as part of another clinical trial in the last 30 days or the drug hasn’t completely cleared your body when you join this study
  • haven’t fully recovered from past treatments unless they are mild, apart from hair loss

Medical conditions

  • have diabetes
  • are taking any medication that blocks an enzyme called CYP3A4 in the 5 days before joining this study
  • have a problem with your digestive system that might affect how you absorb the drug
  • have an inflammation of the lung tissue (pneumonitis) that is active and needs treatment
  • have had major surgery in the 2 weeks before starting alpelisib
  • have problems with your heart, such as a heart attack in the last 6 months, high blood pressure that is not well controlled, angina that is not well controlled, an abnormal rhythm of your heart, congestive heart failure or inflammation of the heart muscle that is causing symptoms
  • have had inflammation of the pancreas (pancreatitis) within 1 year of joining this study
  • have an active hepatitis B or hepatitis C infection
  • have HIV


  • there are any reasons why you might not be able to stick to the study procedures and visits
  • ​you are allergic to alpelisib, fulvestrant, letrozole, goserelin or leuprolide

Trial design

This is an international phase 2 study. The study team need about 160 people to take part including 3 from the UK.

To begin with, the researchers need to check your breast cancer cells for the PIK3CA gene change (mutation). They will look at a tissue sample (biopsy) your doctor took when you had a previous surgery or biopsy. You might need to give a new sample if there isn’t one available.  

You won’t be able to take part in the study if it isn’t possible to identify if you have the mutated breast cancer gene. Your doctor will talk to you about other treatment options.

In this study, people who had letrozole in combination with their CDK 4/6 inhibitor will have fulvestrant. And people who had fulvestrant in combination with their CDK 4/6 inhibitor will have letrozole. So, depending on the hormone treatment you had prior to this, you are put into 1 of the following treatment groups:

  • alpelisib and fulvestrant
  • alpelisib and letrozole

BYLieve Diagram

Alpelisib is a tablet. You take the tablets once a day, every day.

Letrozole is a tablet. You take the tablets once a day, every day.

You have fulvestrant as 2 injections, one into each buttock. You have the injections:

  • twice a month in the first month
  • then once a month

Women who haven’t been through the menopause and some men also have hormone therapy. You have either goserelin or leuprolide. You have this as an injection once a month, every month.  

You have treatment for as long as it is helping you and the side effects aren’t too bad. You stop treatment if your cancer gets worse. Your doctor will talk to you about other treatment options.

Research samples
The researchers will ask for samples of your cancer (a biopsy) that the doctors removed when you had surgery or a previous biopsy. They also ask to take some extra blood samples. Where possible, you have these at the same time as your routine blood tests.

They plan to:

  • look at gene changes (mutations)
  • look at substances called biomarkers to help work out why treatment might work for some people and not for others
  • measure tumour cells that have broken away from the cancer and are circulating in the blood

They will ask you to give extra blood and tissue samples if your cancer gets worse. They will use these to look for additional biomarkers. You don’t have to give these extra samples if you don’t want to. You can still take part in the study.

The researchers might also ask you to give a skin sample (biopsy) if you develop a severe rash.

Hospital visits

You’ll see a doctor and have some tests before you start treatment. The tests include:

  • a physical examination
  • blood tests
  • urine tests
  • heart trace (ECG)
  • heart scan (echocardiogram) or MUGA scan
  • CT scan or MRI scan
  • bone scan

You go to hospital to have fulvestrant. You won’t need to stay overnight.

You see the doctor:

  • 2 to 3 times in the first 2 months
  • once a month after that

At each visit you have a physical examination, blood tests and a heart trace.

You have a CT scan and an MRI scan every:

  • 8 weeks for 18 months
  • 12 weeks after that

When you stop treatment, you see the study team after 1 month for a check up.

After that you see them every 3 months at routine hospital appointments or they might phone you to see how you are getting on.

If you stopped treatment early due to side effects, you see the study team and have a scan every:

  • 8 weeks for 18 months
  • 12 weeks

until your cancer gets worse.

Side effects

As alpelisib is a new drug, there may be some side effects we don’t know about yet. The study team will monitor you during the time you have treatment and you’ll have a phone number to call if you are worried about anything.

The most common side effects of alpelisib include:

  • skin rash or dry skin
  • high levels of sugar in the blood
  • diarrhoea or constipation
  • stomach upset (dyspepsia)
  • feeling or being sick
  • sore or inflamed mouth (stomatitis)
  • tiredness (fatigue) and feeling weak
  • loss of appetite and taste changes
  • weight loss
  • fluid loss (dehydration)
  • taste changes
  • drop in the number of red blood cells (anaemia)
  • tummy (abdominal) pain
  • swollen arms or legs
  • fever
  • leg or arm pain
  • headache
  • difficulty sleeping
  • shortness of breath
  • changes to how the liver works
  • low levels of potassium or magnesium

We have information about:

Recruitment start:

Recruitment end:

How to join a clinical trial

Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Prof Nick Turner

Supported by


If you have questions about the trial please contact our cancer information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:


Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

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