A new path to smarter drug prescribing and funding?

By Laura Blackburn

16 November 2015


Increasing life expectancies are leading to increased risk of the diseases of old age. Of these, cancer is the one of the most common. It is estimated that half the population born after 1960 will be diagnosed with some form of cancer. 

While survival rates for many cancers are improving, treatment failure due to drug resistance or other factors is the harsh reality for many patients. The cancer research community, and industry, are keen to develop new technologies to overcome these challenges, and to offer more personalised treatment to cancer patients. Untangling the cost implications of personalisation will be complex, but essential task.

Circulating tumour DNA – liquid biopsy

One exciting new technology is the analysis of circulating tumour DNA (ctDNA). When cancer cells die, small fragments of DNA are released into the patient's blood stream. Blood samples contain a trove of information (revealed through DNA sequencing technologies) that can be used to monitor response to therapy, emergence of resistance and genetic variation within the tumour.  An advantage of this liquid biopsy is that multiple blood samples can be taken at different times, replacing the need for repeated, invasive tumour biopsies which can be challenging (and sometimes even impossible) to carry out.

A study published recently on using ctDNA to determine genetic basis of resistance to the prostate cancer drug abiraterone demonstrates how ctDNA technology could inform smarter treatment decisions. The study also has implications for a recent funding decision concerning abiraterone, indicating that this novel technology could play a part in informing the decision-making process that decides the availability of life-extending cancer drugs on the NHS. 

The challenge of prostate cancer

Prostate cancer is the most common cancer in men in the UK. Cells within the prostate require male sex hormones, called androgens (these include testosterone) to function and to grow. Androgens bind to the androgen receptor (AR) on the surface of prostate cells and this stimulates cell growth, in the healthy prostate and also in prostate tumours. Many treatments for prostate cancer rely on disrupting this process in some way, either by blocking production of androgens or the receptor and its pathways. 

Abiraterone is currently approved as an end of life therapy for men with advanced prostate cancer who have received first-line hormone therapy and chemotherapy. It works by stopping tissues making testosterone. Abiraterone can extend life by approximately 3-6 months – but it is only effective in a subset of men. In their study, researchers at the Institute of Cancer Research and the University of Trento, Italy, used ctDNA analysis to determine the genetic basis of why the drug works in some men while others are resistant. They analysed blood samples from men when they started treatment with abiraterone and every eight weeks thereafter. 

They found that men who had an increased number of copies of the AR gene within their cancer genome, or one of two specific mutations in the AR gene, were much more likely to be resistant to abiraterone, and had a worse prognosis. Fifteen percent of men in the study developed one of the two AR mutations after they started treatment, which correlated with the drug no longer working after initial success. 

This study demonstrates that analysing the genetic determinants of resistance to an expensive drug can benefit patients, offering a degree of personalisation by ensuring that only those who have a cancer susceptible to abiraterone would be prescribed the drug. Those who are resistant could be offered an alternative treatment strategy. The team behind this study are planning a larger clinical trial with 600 men as much more information is needed to confirm the clinical utility and validity of this test. 

Smarter prescribing, smarter funding decisions?

The development of ctDNA technologies and the greater personalisation of drug prescribing could also have implications for how drug funding decisions are made. In August, the UK’s National Institute for Health and Care Excellence (NICE), which provides guidance for the National Health Service (NHS) on issues including treatment funding, rejected abiraterone for use earlier in treatment, before chemotherapy is given, a refusal based on failure of the drug to perform cost-effectively at this stage according to NICE’s criteria – a  decision nevertheless criticised by some

In principle, any test that determines which patients will benefit from a drug alters the cost of that drug per quality adjusted life year (QALY). On the one hand, if drug prescribing is more selective, then fewer patients receive that drug, so the drug company will not sell as much of that drug and is likely to charge higher prices. On the other hand, the drug is likely to perform very well in patients who do receive it, and as these patients are those most likely to benefit from it they are also likely to live longer, and hence also take the drug for longer. This could have a positive influence on the drug price; as we saw with the breast cancer drug Kadcycla, the price of drugs is not fixed.

Determining how these costs and benefits balance out is a challenge. Health economic studies carried out on other drugs have reported mixed results, so it is clear that well planned, extensive and rigorous analyses are needed to determine whether personalisation is positive or negative in terms of drug efficacy, costs – and most crucially from an NHS funding perspective, cost-effectiveness.

New technologies have the potential to drastically change how some cancer patients are diagnosed, monitored and treated. Whether these technologies will also help to untangle the complex issues surrounding drug funding, or make them even more tangled, remains to be seen. 

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