Based on a seminar given by Professor Janet Dunn, Warwick Medical School

Published February 2012

Stratified medicine - targeting drugs towards the patient’s genetic profile - is the latest buzzword in cancer treatment. In the UK there are 250,000 new cancer cases a year. Breast cancer is the most common form, at 44,000 diagnoses, followed by lung, large bowel and prostate. “Personalised medicine is a medical model of emphasising in general the customisation of healthcare,” clarified Prof Dunn. Treatment is tailored to individual patients using tumour biology and molecular profiling. There are more diagnostic tests available than in the past to help oncologists decide on the appropriate form of treatment. However these tests aren’t yet accessible at initial diagnosis and are usually only available within clinical trials.

Trials conducted at Warwick CTU are evaluating treatment, taking into account patient and tumour characteristics, overall survival, risk of recurrence and response to chemotherapy. Previously doctors have used the Nottingham Prognostic Index (NPI) to establish cancer treatment. This has three main components based on the stage of the cancer:

• Low risk: patient may not get chemotherapy.
• Moderate risk: patient may well receive chemotherapy.
• High risk: patient will have chemotherapy.

Warwick CTU’s research is evaluating the success of the type, combination, duration and sequence of chemotherapy the patient taking part in the trial receives. The type of drug treatment patients on the trial receive depend on whether they are oestrogen receptor positive (ER+ve) and their human epidermal growth factor receptor2 (HER2) status. HER2-positive cancers can be more aggressive than other types of cancer. Approximately 18 per cent of people are HER2 positive. In Warwick CTU’s studies HER2 positive patients receive the drug Herceptin and ER+ve patients are given Tamoxifen or another aromatase inhibitor as well.

A personalised approach to breast cancer can offer the patient more choice as to their care and a greater involvement in their treatment in conjunction with their oncologist. These include decisions such as:

• Whether the patient is to have radiotherapy.
• Whether the patient is to have chemotherapy and if so which order to have it if necessary in conjunction with surgery.
• The type and duration of maintenance therapy.
• Whether or not to have targeted therapy.
• Follow-up type and duration.

Currently the ratio of follow-up patients to new patients in cancer clinics could be as high as 25:1. This is not sustainable and some NHS Hospital Trusts have set a target to reduce this to 5:1 with many clinics discharging patients within three years of initial surgery.

Whilst we are not yet in the era of fully personalised medicine, cancer treatment is changing.

What are the benefits to the patient of having a targeted therapy rather than a cytotoxic drug that doesn’t discriminate between cancer and normal cells? Prof Dunn explained that because targeted therapies are so focused, they usually affect fewer normal cells than cytotoxic drugs. Although targeted therapies do have side-effects these may be less medically significant than those produced by cyctotoxic treatment. Patients have to be aware, however, that targeted therapies do not always kill existing cancer cells and may only prevent them from continuing to grow and divide. Targeted therapies, says Prof Dunn, tend to be viewed favourably by women who have had previous cytotoxic chemotherapy to treat a previous cancer and choose not to undertake it again. The breast cancer trials currently taking place at Warwick CTU are:

• Persephone – duration of Trastuzumab with chemotherapy in women with early breast cancer: six months versus 12.
• ARTemis – Avastin Randomised Trial with neo-adjuvant chemotherapy for patients with early breast cancer.
• OPTIMA – optimal personalised treatment of breast cancer using multiparametric analysis.

The trials are only relevant for patients who have certain tumour characteristics. Both Persephone (HER+ve cancers only) and ARTemis (HER2 –ve cancers only) need a confirmation of HER2 status before patients are allowed to enter the trial. Whereas the OPTIMA trial objectives are, according to Prof Dunn, “to establish a method of selecting patients with hormone sensitive breast cancer to see if they need chemotherapy or not. If the chemotherapy is not needed then patients can start their hormone treatment immediately and will not suffer the additional side-effect of the cytotoxic chemotherapy”.

Whilst we are not yet in the era of fully personalised medicine, cancer treatment is changing to treatment by population selection. To achieve this will require more resources and infrastructure in the NHS, better statistical screening of new bio-markers and improved standardisation in NHS testing centres. Cost-effectiveness and value for money must also be established. Finally, before targeted therapies are universally offered, it’s imperative that trials like those at Warwick’s CTU screen new targeted therapies for long-term toxicity to ensure patient safety.

Professor Janet Dunn is the Deputy Director of Warwick Clinical Trials Unit (CTU) and Head of Cancer Trials at Warwick Medical School, University of Warwick. Her research interests include the evaluation of prognostic and predictive factors in cancer clinical trials, and designing clinical trials to impact on clinical practice.

In 2008 Professor Dunn was awarded National Institute of Health Research Senior Investigator status being one of the inaugural cohort of investigators contributing to applied patient centered research. She has been successful in attracting NIHR National Coordinating Centre for Health Technology Assessment (NCCHTA) grants totallling £6 million for cancer trials at Warwick.