What does participating in REFINE mean to me?

The REFINE trial tests whether giving an immunotherapy drug less-often to patients with advanced cancer results in fewer side effects whilst continuing to be an effective treatment. We think that giving the drugs in this way (‘less-often’ schedule) will be just as effective as the current standard schedule, and may reduce the amount and severity of the side effects. The only way to find out if this is true is to do a clinical trial and compare the two methods. REFINE is a clinical trial that tests these different schedules in patients who have had their first 12 weeks of treatment with immunotherapy and are going to stay on treatment for longer.

We use immunotherapy drugs as a standard treatment option for advanced kidney cancer, bladder cancer, melanoma and some lung cancers. They are usually given by infusion every 3-6 weeks (depending on the specific drug). These drugs work by stimulating the body’s own immune system to fight against cancer cells.

Clinical trials have proven the effectiveness of immunotherapy drugs, such as ipilimumab, nivolumab or pembrolizumab, in the treatment of different cancers. However the best way to give these drugs is not known. 

The trial compares less-often treatment with the standard treatment schedule (for example patients receive treatment with the drug every 8 weeks instead of every 4 weeks). The less-often schedule involves giving the same doses of immunotherapy drugs, but less-often (though the time you remain on this treatment will remain the same).

It is hoped that using a less-often schedule will be more convenient for patients by reducing visits to hospital and side effects whilst still remaining as effective as more frequent treatment. This can also lead to the treatment being more cost effective to the NHS, as the effectiveness of care is maintained but at a lower cost. This means hospital resources are being used more efficiently and more patients can be treated.

What are the most common side‑effects?

You will already have received 12 weeks of treatment with immune checkpoint inhibitor drugs at the point at which you enter the trial.  As with all cancer treatments, you may have some side effects. These differ from person to person and they may be mild or more serious; rarely, some may be life-threatening. It is important that you contact your doctor or nurse straight away if you have any side effects that trouble you. The immunotherapy drugs used in REFINE are the same as the ones you will have already received (and the ones that you would receive even if you were not taking part of the trial).

Because of the way immunotherapy drugs work to fight cancer, they can sometimes cause your immune system to attack your normal organs in any area of your body. This can cause inflammation and sometimes can affect the way your organs work. These problems may happen anytime during treatment or even after your treatment has ended. Below is a list of side effects that have been seen in other patients who have had immunotherapy drugs.

The most common side effects (experienced by equal to or greater than 1 in 10 patients) of the immunotherapy drugs are:

• Decreased appetite
• Nausea
• Feeling fatigued, tired or weak
• Pain in the muscles, bones and joints
• Fevers, chills
• Thyroid gland – this may become underactive and work less well. Your doctor will regularly monitor this using blood tests and you may require thyroid replacement tablets.
• Skin problems – this most commonly causes a rash and/or itching. Vitiligo (loss of pigment in the skin) may also occur
• Bowel problems (colitis) – this can cause diarrhoea and abdominal pain. Severe symptoms have been seen in less than 5% of patients
• Liver problems (hepatitis) – symptoms include fatigue, nausea or vomiting, dark urine, yellowing of the whites of your eyes or skin. Your doctor will regularly monitor your liver function using blood tests. Severe inflammation has been seen in less than 5% of patients

Rarer side effects (less than 1 in 10 patients):

• Constipation
• Vomiting
• Kidney problems (nephritis) – Your doctor will carefully monitor your kidney function using blood tests.
• Hormone gland problems (particularly the pituitary, adrenal and pancreas glands) - Symptoms may include: headaches; extreme tiredness; weight gain or weight loss; dizziness or fainting; feeling cold; constipation. You doctor will monitor the function of your glands using regular blood tests
• Lung problems (pneumonitis) – this may cause shortness of breath, a new or worsening cough or chest pain. Severe symptoms are very rare (in less than 1% of patients)
• Eye problems – this can include blurred or double vision, or other visual problems; also eye pain or redness
• In very rare cases the heart, the blood vessels and the nerves may be affected.

Infusion-related reactions - reactions to the treatment may occur during the infusion itself. This may manifest in a number of ways including fever, chills, pain, headache, rash or low blood pressure. If this occurs, you may need simple medications to control your symptoms and the infusion may need to be slowed down. Very rarely, if the reaction is severe, treatment may need to be permanently discontinued.

What happens after the trial?

Clinical trial results are usually published in specialist medical journals and online libraries of evidence. Results should be made available to anyone who took part in the trial and wants to know the results. The National Institute for Health and Care Excellence (NICE) makes decisions on what treatment should be provided by the NHS. In this case, they would judge whether the new, less-often schedule of care should replace the current standard of care based on a range of evidence, including the effectiveness and cost effectiveness results from clinical trials. 

Further Information

Please find additional information in the links below: