A trial of chemotherapy with or without everolimus for HER2 breast cancer that has spread outside the breast (BOLERO 1)

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

Cancer type:

Breast cancer




Phase 3

This trial is looking at chemotherapy and everolimus (Afinitor) for breast cancer that is HER2 positive and is locally advanced, or has spread to another part of the body (metastatic or secondary breast cancer). It is for women who have not yet had any treatment for advanced breast cancer.

Some breast cancers have large amounts of a protein called HER2 on the surface of the cells. These cancers are ‘HER2 positive’ and can be treated with a drug called trastuzumab (also known as Herceptin), which targets the HER2 protein.

You may have Herceptin with chemotherapy. Paclitaxel is one of the chemotherapy drugs commonly used.

Sometimes a drug can stop working, even though the cancer responded to it at first. Doctors call this resistance Open a glossary item. Researchers want to find ways of treating breast cancer that has become resistant to Herceptin. We know from laboratory research that a drug called everolimus (also known as RAD001) may help.

Everolimus is a drug that was first developed for people who have had a heart or kidney transplant. It helps to damp down the immune system to stop the body rejecting the new organ. But everolimus may also help to stop cancer cells growing.

The aim of this trial is to see if having everolimus at the same time as Herceptin and paclitaxel helps women with HER2 positive breast cancer that has spread outside the breast.

Who can enter

You can enter this trial if you

  • Are a woman with breast cancer that is locally advanced or has spread and is HER2 positive
  • Have areas of cancer that the trial doctors can measure
  • Have satisfactory blood test results
  • Are well enough to take part in the trial (performance status of 0 or 1)
  • Are willing to use reliable contraception during the trial and for 4 weeks after if there is any chance you could become pregnant
  • Are at least 18 years old

You cannot enter this trial if you

  • Have cancer that your doctors think can be cured with surgery
  • Have cancer that has spread to your brain
  • Have already had treatment for breast cancer that is locally advanced or has spread – this does not include the treatment you had for early breast cancer unless the cancer came back less than a year after finishing Herceptin or chemotherapy
  • Have a build up of fluid anywhere in the body such as the lungs (pleural effusion Open a glossary item) or abdomen (ascites Open a glossary item)
  • Have had radiotherapy to more than a quarter of your bone marrow Open a glossary item in the last 4 weeks
  • Already have symptoms of nerve damage, such as pins and needles or numbness in fingers or toes (peripheral neuropathy)
  • Have already had any drug that works in a similar way to everolimus - the trial doctor can advise you about this
  • Are known to be sensitive to any of the drugs in this trial
  • Take drugs to prevent blood clots
  • Have a peptic ulcer Open a glossary item or any condition that could make it difficult for you to absorb tablets
  • Have ever had a heart attack, or have other heart problems that are a cause for concern
  • Have high blood pressure that cannot be controlled with medication
  • Have an infection that cannot be controlled or any other medical condition that could affect you taking part in the trial
  • Are pregnant or breastfeeding
  • Are known to be HIV positive

Trial design

This is an international study. It will recruit more than 700 people in different countries. It is a randomised trial. Everybody taking part will be put into 1 of 2 treatment groups by computer. Neither you nor your doctor will be able to choose a group, or know which group you are in. This is called a ‘double blind trial Open a glossary item’.

Everybody taking part will have Herceptin and paclitaxel. You have treatment on one day each week. Every 4 week period is called a cycle of treatment. In the first 3 weeks of each cycle, you have Herceptin and paclitaxel. In the 4th week, you have just Herceptin. You have both drugs through a drip into a vein. It takes about 2 hours each time.

  • Women in group 1 also take everolimus tablets every day
  • Women in group 2 take dummy tablets (placebos Open a glossary item)

You take the tablets at the same time each day. You must not eat grapefruit, star fruit, pomegranate or Seville oranges (or drink their juices) during the trial. This is because they can affect the way everolimus works. And you can’t take some herbal medicines such as St John’s wort.

As long as you don’t have bad side effects, you can carry on having the treatment for as long as it helps you.

Hospital visits

You will see the trial doctors and have some tests before you start treatment. The tests include

  • Physical examination
  • Blood and urine tests
  • Heart trace (ECG Open a glossary item)
  • Tests to see how well your lungs are working (lung function tests Open a glossary item)
  • Heart scan (MUGA Open a glossary item or Echocardiogram Open a glossary item)
  • CT scan
  • Bone scan
  • MRI scan
  • X-rays of your bones
  • Pregnancy test (if there is any chance you could become pregnant)

You go to hospital every week to have treatment. Every 8 weeks, you have a CT or MRI scan, a bone scan, and bone X-rays. And you have a MUGA scan or echocardiogram every 3 months.

When you finish treatment, you will go back to see the trial doctors within 4 weeks. After that, the trial team phone you to see how you are every 6 months for about 5 years.

If you stop having treatment for any reason other than your cancer getting worse, the trial team will ask you to carry on having scans until the cancer starts to grow again.

Side effects

The possible side effects of everolimus include

If you have had hepatitis B in the past, this could become active again.

Rarely, everolimus can cause swelling (inflammation Open a glossary item) of the lungs, leading to a cough and shortness of breath.

The side effects of Herceptin and paclitaxel include

  • Allergic reactions
  • Fever and chills
  • Sickness
  • Headaches
  • A drop in the number of blood cells causing an increased risk of infection, bruising or bleeding problems, tiredness and shortness of breath
  • Heart changes
  • Pain in muscles and joints
  • Hair loss

There is more information about the side effects of Herceptin and paclitaxel on CancerHelp UK.

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

Dr Charles Swanton

Supported by

NIHR Clinical Research Network: Cancer

Questions about cancer? Contact our information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

Oracle 4540

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

Harriet wanted to try new treatments

A picture of Harriet

“I was keen to go on a clinical trial. I wanted to try new cancer treatments and hopefully help future generations.”

Last reviewed:

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