The Kadcyla debate and the future of targeted cancer drugs

Julia Swallow, University of Leeds

Recently in the UK news, there has been extensive discussion about the cost-effectiveness and funding of new treatments for cancer and particular sub-types of cancer. Drugs, which are developed to effectively target particular sub-types of cancer such as human epidermal growth factor 2 (HER2) positive breast cancer, have the potential to improve survival rates and extend quality of life, bringing renewed hope for patients and their families. However, these drugs are expensive to manufacture and for the NHS to fund and it is not always the case that they extend life or quality of life for a significant length of time. This is because certain sub-types of cancer have a complex biology and they may become resistant to treatments. It is therefore a complex process measuring the cost-effectiveness of these new treatments in terms of improved survival and quality of life: the current framework for justifying cost is based on whether the drugs have clear and measurable benefit for patients. In this post, we will discuss the complexities of measuring cost-effectiveness for these types of treatments by looking at the recent debate around NHS funding for Kadcyla (trastuzumab emtansine), a targeted breast cancer drug.

Changing practices around funding cancer drugs

The National Institute of Clinical Excellence (NICE) approve cancer drugs for funding by the NHS through their Technology Appraisal system. Recommendations for funding by the NHS are based on the availability of adequate clinical and economic evidence: ‘clinical evidence shows how well the medicine or treatment works and economic evidence shows how well the medicine or treatment works in relation to how much it costs the NHS’. In other words, NICE evaluate whether the drug represents value for money. The NHS has a legal obligation to fund all medicines and treatments recommended for use by NICE but there may be instances where NICE do not recommend a drug to be funded by the NHS based on cost-effectiveness and this is where the Cancer Drugs Fund (CDF) becomes important. The CDF was set up by the UK government in 2011 however, it is not UK wide and serves only England. As yet there is no equivalent of the CDF in Northern Ireland, Wales or Scotland. The CDF was set up to fund medicines and treatments not routinely available on the NHS, including those not recommended by NICE due to questionable cost-effectiveness or uncertain clinical effectiveness However, as argued by NICE, this model of the CDF created ‘unsustainable financial pressure’ as it was unclear how and when drugs should be transferred out of the fund and into routine NHS commissioning. Thus, in July 2016, following a 12-week public enquiry initiated by NICE, NICE and NHS England relaunched the CDF to include amongst other things, a set time for new drugs to be definitively approved or rejected by NICE. Following the relaunch of the CDF however, over the past year, NICE has rejected funding for several targeted cancer drugs and called for the manufacturers to offer them at a lower price. For example, Kadcyla has been provisionally rejected by NICE, and NHS England have decided to remove it from the Cancer Drugs Fund on the grounds that it is not cost-effective.

The Recent Kadcyla debate

Kadcyla is used for advanced or metastatic breast cancer in people with human epidermal growth factor receptor 2 (patients who are HER2 positive) who may no longer be responding to Herceptin. In 2012, Genentech conducted an international, randomised clinical trial, EMILIA, which revealed that Kadcyla extended life by approximately six months in comparison to other treatments. Kadcyla was first rejected by NICE in November 2015 as it was deemed too expensive and NHS England decided to remove it from the list of treatments made available through the Cancer Drugs Fund. The threshold for approving a drug by NICE is £50,000 per patient per year for an end of life drug and the estimated cost of Kadcyla is £90,000 per patient, per year according to manufacturing company Roche. In response to its rejection, Breast Cancer Now, which is the largest breast cancer charity in the UK, lobbied the UK government and organised a petition requesting Roche to lower the price of their product. Their efforts were successful and in November 2015 the drug was reinstated by the Cancer Drugs Fund.

However, on 29th December 2016, the decision was once again overturned and NICE issued its draft guidance recommending that Kadcyla should be provisionally rejected on the grounds that is not cost-effective. Breast Cancer Now started a petition, which received over 80,000 signatures and with the aid of the All-Party Parliamentary Group on Breast Cancer, the case of Kadcyla was debated in parliament on 26th January 2017. The case drew a number of individuals and their families to testify for the benefits of the drug in the advanced stages of the disease, arguing primarily that it not only extends life and gives patients ‘more time’ but also provides patients with hope for the future when Herceptin may no longer be effective. This was echoed by the Chief Executive of Breast Cancer Now, Baroness Delyth Morgan, who stated when interviewed for BBC News, ‘Kadcyla offers significant and precious extra time for women with incurable cancer in great need of hope, and we mustn’t let it slip away.’

Whilst the experiences of patients constitute one aspect of the discussion, scientific evidence also demonstrates that Kadcyla significantly improves the lives of women living with breast cancer. This makes the case of Kadcyla particularly contentious as evidence from trials suggest that those prescribed the drug have ‘longer overall survival, extending life by an average of 9 months, as well as longer progression-free survival than do patients on other cancer drugs’ (The Lancet 2017). The Lancet commentary also argues that the decision to provisionally reject Kadcyla is based purely on cost and fails to acknowledge the effectiveness of the treatment ‘for a patient group with so few options’. The commentary concludes by stating that ‘NICE must move beyond price as a decision-making basis for treatment’. Balancing cost alongside quality and extension of life is therefore at the centre of concerns over the provisional rejection of Kadcyla.

The relevance of the Kadcyla case to our research

Measuring cost-effectiveness and understanding the complexity of patients’ treatment decisions based on their hopes and expectations is complicated as targeted treatments move from bench to beside. But this case suggests that cost-effectiveness is not a purely scientific matter: patients and their families as well as charities and drugs companies can influence what is understood as ‘cost-effectiveness’ when decisions are made about funding treatments. These debates also shift patients’ and practitioners’ hopes and expectations for the availability of targeted and expensive therapies in the future, bringing new kinds of responsibilities in terms of accessing and sourcing novel treatments and therapies. In particular, some kinds of patients are playing a new role here in lobbying for drugs and participating in research studies particularly as there is an increasing emphasis on public and patient involvement in scientific research and healthcare policy. This has the potential to create a set of highly knowledgeable patients with the resources to contribute to, and engage with, key debates concerning cost-effectiveness. To understand the future for targeted medicine based on genomics we need to appreciate how notions of cost-effectiveness are evolving in this context, as well as thinking carefully about the new kinds of responsibilities that patients involved in lobbying are taking on in this new era of targeted or personalised medicine. We will be following the case of Kadcyla over the coming weeks as NICE issues its final guidance and continuing to reflect on the implications of these developments.