In 2023, Chris Booth (Montreal, 49 years old), director of the Division of Oncology Care and Epidemiology at the Queen’s Cancer Research Institute (QCRI), and other oncologists from around the world launched the initiative Common Sense Oncology (Common Sense Oncology). They wanted to provoke a public debate about a worrying trend in oncology. Although many cancer treatments have saved the lives of many patients or prolonged their lives in comfort, there are more and more that offer small benefits for a very high price, a lot of toxicity and keeping patients in the hospital for a long time at the end of life, when every hour is even more valuable.
In his studieswarns that many current treatments do not meet the usual thresholds for assessing the usefulness of drugs, such as offering a year of quality life for $50,000 or even $100,000. He also points out that drugs are evaluated on criteria such as the amount of time they stop tumor growth (progression-free survival), which in many cases is not related to increasing months or years of survival. Between 2003 and 2023, 48% of cancer drugs approved by the FDA, the agency that regulates drugs in the US and serves as a reference for other agencies around the world, were approved based on progression-free survival rather than overall survival.
In a recent article Presented at the annual meeting of the American Society of Clinical Oncology, they recalled that, over the past 30 years, clinical trials of cancer drugs, which were previously supported more by government money and the initiative of researchers, have come to be financed 85% by the pharmaceutical industry. In a conversation by video call, Booth states that “oncologists have known this reality for a long time and a large majority would agree on the need to find solutions”, but they needed a space to talk openly about these problems and improve the situation of their patients and their families.
Ask. 85% of trials are funded by industry, but many oncologists and government science funders say it cannot be done any other way because only pharmaceutical companies have the large amounts of money needed.
Answer. I agree and disagree. It is important to recognize that many of our excellent treatments and some of the best clinical trials have been done in collaboration with the pharmaceutical industry. I don’t want to give the impression that we are anti-industry. The problem is that the pendulum has swung so far to one side that the entire cancer research ecosystem is now largely funded by the pharmaceutical industry, meaning that the studies designed, launched and funded must align with the pharmaceutical companies’ primary mandate, which is to make a profit for shareholders. Sometimes the mandate to make things better for patients and the industry mandate align, but not always.
We need to create a place and alternative sources of funding. We need a renewal of investment in clinical cancer research by government funding agencies. I also think there is a role for the health system, to fund clinical trials that address questions that are important to patients, but that are perhaps of less interest to industry. For example, there is a lot of interest right now in de-escalating treatments, reducing the intensity of treatments, reducing side effects for patients. We have examples. Their results are maintained and money is saved for the health system. These trials will not be of interest to the pharmaceutical industry, but they will be of great interest to patients, families and the health system.
P. One can understand the industry’s incentives to seek approval of drugs on the basis of progression-free survival rather than overall survival, but why would regulators accept that?
R. Regulators have a very difficult job because they are trying to balance a number of competing priorities. There is a constant tension between approving treatments quickly, so that they reach patients as soon as possible, but also making sure that they are good treatments.
Maybe we could have an initial regulatory approval based on some kind of surrogate endpoint. [mediciones para ver si el medicamento actúa aunque no haya dado tiempo a ver si prolonga la vida] to provide patients with access to the drug while we await long-term data to confirm the overall survival benefit and confirm whether the drug obtains full regulatory approval.
I also think that in our field in general, including regulators, we were perhaps too optimistic 15 years ago when progression-free survival started to be used in phase three trials. [los grandes ensayos justo antes de la aprobación final de un fármaco]It was never invented for phase three trials. It was invented to guide early drug discovery in phase one and phase two trials, to give a signal of activity and to let researchers and the pharmaceutical industry know whether this is worth trying in a phase three setting. It was thought that these benchmarks would serve to predict that the patient was going to live longer and better and that we would get answers quicker.
We’ve learned, ten years later, that maybe that wasn’t as safe as we thought. We’ve seen that progression-free survival is a good surrogate for overall survival in some limited circumstances, but in the vast majority of circumstances, it doesn’t predict whether someone will live longer or better. And that’s really important because these treatments are not benign. The other reason we started using progression-free survival is that we thought we would get answers more quickly. And again, ten years later, we’ve learned that it saves some time, but the estimates are that it probably saves less time than we thought, probably less than a year before we get the final answer.
Considering that at least half of clinical trials are designed to slow tumor growth that you see on a CT scan, which is progression-free survival, and not to help people live longer, we should think about whether we are comfortable with a cancer research ecosystem and that model of patient care. The answers are complicated, but I think it’s at least worth having the conversation, being humble and acknowledging that maybe some of our treatments aren’t as helpful as we thought.
P. They have also published data indicating that more expensive therapies have less benefit than cheaper ones. This inverse correlation is strange.
R. It’s a totally broken model. Last month, we published an article in Lancet Oncology which outlined health spending on cancer drugs for the entire province of Ontario. Ontario is the largest province in Canada, with a population of 15 million people, with a single-payer health care model. We found that the rate of increase in spending on cancer drugs is staggering. It’s increasing at a rate of 15% per year, while all other health spending is increasing at a rate of 5% per year. And about half of all we spend on cancer is on cancer drugs.
The second economic point you’ve already mentioned is the fact that in cancer there is no relationship between how well a drug works and its price. If anything, the drugs with the smallest benefit have the highest price.
The third economic finding is th
at the entire global pharmaceutical sector is turning to cancer. We have analysed the ten largest pharmaceutical companies in the world over the last decade and their share of revenue from sales of cancer treatments has grown relative to that of all other diseases.
In principle, that might be good news for oncologists and people with cancer, but firstly, there are other public health issues that require investment, innovation and new treatments. And secondly, more money is not always good. The whole system is addicted to the money that comes from selling cancer drugs. There are these enormous financial pressures that, whether we acknowledge it or not, shape much of the cancer system. This is something we should at least acknowledge and discuss.
P. They also mention that there is a point in the course of the disease when the investment in treatments would be more useful if it were dedicated to palliative care. But I suppose there are many people who consider this to be throwing in the towel or giving up on a loved one.
R. What you’re talking about is the war narrative that emerged from Richard Nixon’s war on cancer in the 1970s. It creates some problems in the public perception of oncology, which is always a struggle and a battle. That perception, which pushes you to keep fighting, leads to decision-making, especially near the end of life, that can lead some patients to receive treatments they otherwise would not have wanted.
Neither I nor the Common Sense Oncology initiative believe that we have the answers for every individual patient about what treatment is right for them, but we do believe that there is room for reflection on the benefits of some of those treatments, especially when they are quite small and have a lot of side effects, especially near the end of life. I think we can do a better job of empowering patients to have the information that they need to make these decisions, which are obviously very difficult.
P. In addition, these treatments are extremely expensive and sometimes only prolong life slightly or not at all.
R. In the US, a cancer diagnosis is a leading cause of bankruptcy, and it is much worse in low- and middle-income countries, where the cost of cancer care is paid entirely by the patient and family. It is tragic enough to have a cancer diagnosis and not have a cure, without having to put a family into debt for generations to receive a very toxic treatment with little benefit.
In systems with public health care, the system takes on some of the financial toxicity, but there is also the paradox of the last six months of life. In systems like the Spanish or Canadian, after going through previous treatments, there may be a treatment available that may cost the health system a hundred or two hundred thousand dollars, and it might help the patient live a few more weeks or it might not. It has side effects and it requires them to spend a day each week in the chemotherapy unit. The paradox is that we have a system that provides that element of care quite easily, but it is almost impossible for the system to offer that patient, who may feel alone, vulnerable, scared, enough psychosocial, mental health or nursing support to enable them to live at home with dignity and comfort at the end of their life.
You can follow THE COUNTRY Health and Wellbeing in Facebook, X and Instagram.
#Chris #Booth #oncologist #war #narrative #cancer #leads #patients #receive #treatments #wanted
