The end-of-life care conundrum

Research advises against aggressive cancer treatment at the end-of-life stages of the disease. At the same time, the pharmaceutical industry is creating a greater number of oncology treatments that could provide breakthroughs for patients where none previously existed. Ben Hargreaves examines why there is no easy answer to the question of when palliative care is the right option for patients.

The difficult conversations are often the most important ones. This is true of the end-of-life conversations that need to take place between patients and medical professionals. Once no cure can be found for a patient’s condition, decisions must be made about what is the most suitable path forwards. Over recent years, there has been a growing consensus that using chemotherapy and aggressive treatments towards the end-of-life should be avoided, where possible, due to the lower quality of life reported.

Though it may be immediately apparent, it is worth noting that this is an extremely difficult decision to reach, and is one that must take place between a patient and their healthcare professional. Of the many reasons for this, the understanding of what constitutes quality of life and the importance of additional time bought through continued treatment is subjective to the individual. However, the importance of simply having this discussion has been raised again by a significant change in the way in which some patients are now being treated at the end-of-life stage of cancer.

The rise of immunotherapies

Over the last few years, immunotherapies have emerged and become one of the most important new tools against cancer. The most prominent of such therapies are immune checkpoint inhibitors, such as the PD-1/PD-L1 therapies that have become some of the best-selling treatments across the industry. The reason they have become so widely prescribed is their ability to extend life in patients where there are few other options. Research found that the average five-year survival rate for patients receiving one such treatment, Keytruda (pembrolizumab), increased from 5.5% to 15%.

The success of such treatments has, however, raised another question, after researchers discovered that though chemotherapy-usage at the near-end-of-life stage had reduced, this could be because more patients had been transitioned onto immunotherapies. The study that emerged from scientists at the Yale Cancer Center, working in collaboration with researchers from Flatiron Health, concluded that there is no difference between the overall use of systemic anti-cancer therapy at the end-of-life stage since 2015.

Kerin Adelson, associate professor of medicine, chief quality officer and deputy chief medical officer for Smilow Cancer Hospital, and senior author on the study, outlined, “The approval of multiple new immunotherapy agents has engendered a great replacement phenomenon, substituting immunotherapy for chemotherapy.”

In terms of statistics, the researchers found that rates of treatment within 30 days of death among all cancer types combined did not change (39% in 2015 and 2019), with similar statistics seen within 14 days of death (17% in 2015 and 2019). What did change was the use of chemotherapy (26% in 2015 and 16% in 2019), and the increase in the delivery of immunotherapy (5% in 2015 and 18% in 2019). According to the researchers, there were actually increases in treatment for patients at the end-of-life stage in non-small cell lung cancer and urothelial cancers – going against the movement to decrease the use of aggressive treatments at the end-of-life stage.

“Increases in the use of targeted therapies may have interfered with our ability to achieve earlier palliative care integration and reduction in acute care utilisation. More research is needed to determine if this change has affected the way end-of-life care is provided,” Adelson concluded.

Quality of life

This is of such importance because the consensus that has been reached across the healthcare industry is that attempts to reduce the intensity of end-of-life care should be a priority. Flatiron, one of the partners of the study, suggested in research that had similar findings in 2020 that the reason immunotherapies are becomingly increasing used at the end-of-life stage is that they have a favourable tolerability and high expectations for efficacy.

However, the authors concluded that the emergence of such treatments had led to “the tendency to use immunotherapy in EOL (end-of-life) settings where less aggressive approaches may be preferable.” The attempt to avoid more aggressive treatments has emerged due to the research that has found that chemotherapy delivered at the end-of-life is closely linked to inconvenience and unnecessary cost to both the patients and the healthcare system.

For patients, receiving aggressive treatment towards the end-of-life creates numerous challenges, as such treatment could cause adverse side-effects, prevent the patient from engaging in meaningful life review and preparing for death, and preclude entry into a hospice, one study found. The additional cost can arrive for patients through the increased care received, and for the healthcare system due to the expense of continued treatment, especially with newer forms of therapy, such as immunotherapy.

The alternative is palliative care, which Cancer Research UK states could help some individuals live longer and more comfortably, and may still involve receiving some form of cancer treatment to reduce or remove some symptoms from tumours. Determining which patients to switch to palliative care is a decision reserved for the patient themselves and their healthcare professional. Despite broad advisories from patient associations and professional societies being helpful to provide a framework, individuals will have different ideas of when taking the palliative care route is suitable.

For instance, one key determiner of treatment value in the UK is made based on ‘Qualify Adjusted Life Year’ (QALY), which has become well-known as a tough measure of the cost-effectiveness of a treatment. However, for a patient living at the end-of-life, the perception of time itself can be understood to have fundamentally changed when compared to their previous healthy phase, a study discovered. Research such as this underlines the complexity of the area and the difficulty of assessing it with objective measures.

Direction of treatment

For both patients and healthcare providers, a discussion of the question of how best to provide care for those at the end-of-life with cancer is never going to emerge with easy answers. The importance of having the conversation is likely only going to grow in the short- and long-term, as the pharmaceutical industry continues to prioritise and successfully develop treatments against cancer. Oncology is an area where a number of breakthrough treatments have emerged, from the previously mentioned immunotherapies to CAR-T therapies, with the latter resulting in remission for some patients where no curative treatment had been previously possible. With more effective treatments, and therefore more hope of receiving a cure, holding end-of-life discussions may become even more difficult, but remains a vital part of providing care for patients facing limited options.