Chris Booth, oncologist: ‘The war narrative around cancer leads some patients to receive treatments they would not have otherwise wanted’

The doctor is one of the promoters of the Common Sense Oncology initiative, which warns that many anti-cancer drugs offer little to no benefits

Chris Booth
Oncologist Christopher Booth.C.B.

In 2023, Chris Booth — the director of the Division of Cancer Care and Epidemiology at Queen’s Cancer Research Institute (QCRI) — and other oncologists around the world launched the Common Sense Oncology initiative. They wanted to provoke public debate about a worrying drift in oncology. Although many cancer treatments have saved the lives of patients or prolonged their lives with quality of life, there is a growing number that offer few benefits for a very high price, a lot of toxicity, while keeping patients in hospital for a long time at the end of life, when every hour is even more valuable.

In his studies, Booth, 49, warns that many of the current treatments do not meet the usual thresholds for assessing the usefulness of medications, such as offering one year of quality life for $50,000 or even $100,000. He also points out that drugs are evaluated based on criteria such as the amount of time they stop tumor growth (progression-free survival), which, in many cases, is not related to whether the paitent survived for more months or years. Between 2003 and 2023, 48% of drugs for cancer treatments approved by the FDA — which serves as a reference for other regulators around the world — were approved based on progression-free survival and not on total survival.

In a recent article presented at the annual meeting of the American Society of Clinical Oncology, the Common Sense Oncology initiative recalled that, in the last 30 years, clinical trials of cancer drugs — which were previously supported more by government moneys and the initiative of researchers — has become 85% funded by the pharmaceutical industry. In a video call conversation, Booth states that “oncologists have known this reality for a long time and a large majority would agree on the need to look for solutions,” but they needed a space to talk openly about these problems and improve the situation of their patients. and their families.

Question. Eighty-five percent of trials are financed by the industry, but many oncologists and government officials responsible for funding science say that 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 conducted in collaboration with the pharmaceutical industry. I don’t want to give the impression that we are against the industry. The problem is that the pendulum has swung so far one way that the entire cancer research ecosystem is now largely funded by the pharmaceutical industry, meaning that studies designed, launched and funded must align with the core mandate of pharmaceutical companies, which is to obtain profits 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 funding sources. We need a renewal of investment in clinical cancer research by government-funded agencies. I also think there is a role for the healthcare system to fund clinical trials that address questions that are important to patients, but that are perhaps of less interest to the 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 of this. The results remain the same and the health system saves money. 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.

Q. It’s understandable why the industry would seek drug approval based on progression-free survival and not overall survival, but why would regulators accept that?

A. 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 ensuring that they are good treatments.

Perhaps we could have an initial regulatory approval based on some kind of surrogate endpoint [measurements to see if the drug works even if it hasn't had time to see if it prolongs life] so that patients have access to the drug while we wait for long-term data to confirm the overall survival benefit and confirm whether the drug gains 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 began to be used in Phase 3 trials [the large trials just before a drug’s final approval]. It was never invented for Phase 3 trials. It was invented to guide early drug discovery in Phase 1 and Phase 2 trials, to give a signal of activity and let researchers and the pharmaceutical industry know if this was worth trying in a Phase 3 setting. It was thought that these references would serve to predict that the patient would live longer and better and that we would get answers faster.

We have learned, 10 years later, that perhaps that was not as indicative as we thought. We have seen that progression-free survival is a good surrogate for overall survival in some limited circumstances, but, in the vast majority of circumstances, it does not 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, 10 years later, we’ve learned that it saves some time, but estimates indicate 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 the growth of the tumor seen on a CT scan, which is progression-free survival, and not to help people live longer, we should think about whether we feel comfortable with a cancer research ecosystem and that model of patient care. The answers are complicated, but I think it’s worth at least having the conversation, being humble, and acknowledging that maybe some of our treatments aren’t as helpful as we thought.

Q. You have also published data indicating that more expensive therapies have less benefit than cheaper ones. This inverse correlation is strange.

A. It is a totally broken model. Last month, we published an article in Lancet Oncology that described health spending for cancer drugs for the entire province of Ontario. Ontario is Canada’s largest province, with a population of 15 million people, with a single-payer healthcare model. We found that the rate of increase in spending on cancer drugs is staggering. It is increasing at a rate of 15% per year, while the rest of health spending is increasing at a rate of 5% per year. And about half of everything we spend on cancer is for anti-cancer drugs.

The second economic point that you have already mentioned is the fact that in cancer, there is no relationship between how well the drug works and its price. If anything, the drugs with the smallest benefit have the highest price.

The third economic finding is that the entire global pharmaceutical sector is turning to cancer. We have looked at the 10 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 could be good news for oncologists and people with cancer, but firstly, there are other public health problems that require investment, innovation and new treatments. And secondly, more money is not always good. The entire system is addicted to the money that comes from the sale of cancer drugs. There are enormous financial pressures that, whether we recognize it or not, shape much of the cancer system. This is something we should at least acknowledge and discuss.

Q. You also mention that there is a moment 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 many people would consider this throwing in the towel or giving up on a loved one.

A. What you mention 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 for the fight to continue, leads to decision-making, especially near the end of life, that can lead some patients to receive treatments they would not have otherwise wanted.

Neither I nor the Common Sense Oncology Initiative believe we have the answers for each individual patient about which treatment is right for them, but we think there is some room for reflection on the benefits of some of those treatments, especially when they are quite small and have many secondary effects, especially near the end of life. I think we can do a better job of empowering patients to have the information they need to make these decisions, which are obviously very difficult.

Q. These treatments also involve enormous costs that sometimes do little or nothing to prolong life.

A. In the U.S., 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 out-of-pocket. entirely by the patient and family. It is tragic enough to have a cancer diagnosis and it not be curable, without also putting your family in debt for generations just to receive a very toxic treatment with little benefit.

In systems with public health care, the system assumes 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 ones, after going through previous treatments, there may be a treatment available that may cost the health system $100,000 or $200,000, and it could help the patient live a few more weeks or maybe not. It has side effects and requires the patient to spend one 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 allow them to live at home with dignity and comfort at the end of their life.

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