by ecancer reporter Clare Sansom

Personalised or stratified medicine, when defined as drugs directed to specific molecular targets that are present in some, but not all, patients with a particular disease is one of the most exciting trends in modern pharmacology and medicine.

Oncology was the first discipline in which personalised therapies came into regular clinical use, and these drugs are already helping many cancer patients survive and thrive.

However, there are also many cancer patients whose tumours turn out to be unsuitable for any of the available personalised therapies, and whose only pharmacological options are chemotherapies that are often toxic or ineffective.

The ‘hype’ surrounding personalised oncology in recent years may have led to an over-emphasis on molecular treatments for the most tractable subset of patients, at the expense of the others and of less glamorous but more cost-effective public health initiatives in cancer prevention.

This and other ethical dilemmas raised by personalised medicine were discussed in a fascinating lecture given by Joshua Hordern of the Oxford Healthcare Values Partnership on Thursday 5 October at Hughes Hall, Cambridge.

The talk was sponsored by the PHG Foundation, a think tank on technology and healthcare based in Cambridge.

It drew on a research project in the ethics of personalised medicine that involved a collaboration between the Healthcare Values Partnership and the MRC stratified medicine consortium in Colorectal Cancer (S-CORT), results from which have recently been published in a special issue of the journal The New Bioethics.

Despite no scientific or medical training – Hordern is a theologian and ethicist who lectures in Christian ethics in the Faculty of Theology and Religion at Oxford – he managed to hold the attention of a largely scientific audience throughout a long and quite complex lecture.

He began by setting out some of the general ethical dilemmas raised by stratified medicine in terms of data sharing and participation – to what extent does medical data ‘belong’ to the patient concerned, to his or her physician, or to the healthcare system? – and of equity and value, before turning at more length to the problems of the ‘molecularly unstratified’ patient.

In the case of cancer, personalised medicines should be prescribed alongside ‘companion diagnostics’ to ensure that they are only given to patients whose tumours carry the correct genetic signature and who are therefore likely to benefit from the treatment concerned.

Sometimes, the patients who can benefit from a new therapy are in a small minority; Hordern cited a case in gastric cancer where 70 patients had to be screened for one to be enrolled in a clinical trial.

In such trials ‘unstratified’ patients are rarely assigned to a trial subgroup: far more often, they are left to receive the current standard of care.

Patients in such a group, whether it is proportionally large or small and however they are treated, may feel ‘left out and left behind’ with access to the most ‘hopeful’ treatments closed down.

A representative of the charity Bowel Cancer UK commented that the ‘unstratified’ colorectal cancer patients they talk to feel it deeply: “it is a deeply distressing experience to learn that stratification is not for them”.

One way to reduce these problems must be by careful communication: removing the ‘hype’ around personalised drugs will reduce the disappointment felt by unstratified patients as well as by those stratified ones who try the drug with disappointing results.

Clinicians and researchers as well as patients can suffer from over-hyped personalised drugs, feeling stressed by the pressure to succeed through promised ‘miracle cures’.

Perhaps unsurprisingly for a theologian, Hordern ended his talk by stressing the need for compassion in all dealings with patients, and, particularly, the need to treat each one as an individual.

Many problems arise from thinking of the personalised drugs as ‘Holy Grails’: however innovative they are, older, less sophisticated and less ‘fashionable’ drugs, therapies and public health approaches still have value and should not be neglected.

All clinical trials should include a detailed examination of the patient experience; one example of a trial where this has been incorporated into the design is FOCUS4, a multi-arm trial of stratified drugs for colorectal tumours bearing relevant mutations.

In summary, the undoubted promise of personalised medicine to benefit the whole oncology community will only be fully met with a holistic emphasis on all patients as individuals and with compassion as a core goal.  

Reference
The New Bioethics 23(1) (2017): Personalised Medicine: the Promise, the Hype and the Pitfalls. Journal special issue.