We are paying far too much for cancer drugs that don’t work very well. Time for a change

By Jerome Burne

Most pharmacological treatments are Janus faced. They come with both benefits and risk, in some cases severe risk. Cancer drugs are more likely to cause unpleasant side effects than most. One result is that a proportion of patients seek out non-drug ‘lifestyle” treatments such as changing your diet, taking regular exercise and supplements, reducing stress and improving your sleeping patterns. 

The majority of doctors still regard all this as a waste of time, lacking good evidence from ‘gold standard’ randomised controlled trials (RCTs) and possibly dangerous. But airily dismissing it is getting harder, thanks to a recent well-informed critique of the evidence supporting the drugs and growing use of a broader lifestyle approach. 

This coming weekend, for example, a large online conference with top researchers and clinicians among its 40 speakers will be presenting the evidence that the lifestyle approach can not only support conventional treatments but that it also targets the metabolic (how our bodies use energy) changes in cancer cells, something that conventional treatments ignore. It’s organised by the UK charity Yes to Life (COI: I am a trustee) with the support of others such as Penny Brohn UK and Maggie’s Centres. 

Two of the speakers are international experts on the ways the low carb ketogenic diet can help to treat cancer – Valter Longo, Professor of Gerontology and Biological Science at the University of Southern California and Thomas Seyfried Professor of Biology at Boston College. 

Devastating critique of cancer drug regulation 

Other experts come from the University of California San Francisco, the Center for Functional Medicine at the Cleveland Clinic in Ohio, and the Center for the Integrative Oncology, Paracelsus Hospital, Switzerland. They will be talking about the benefits of combining cancer drugs and lifestyle changes – known as integrative medicine.

This heavyweight support comes shortly after a devastating critique of the safety and effectiveness of conventional cancer drugs appeared in a book called ‘Malignant: How Bad Policy and Bad Evidence Harm People with Cancer’ by Dr Vinayak Prasad, a senior oncologist and expert in public health at Oregon Health and Science University. He ignores any alternatives but makes it clear major reform is needed if conventional treatment is to continue claiming it is evidence-based. 

His exposé makes shocking but carefully researched claims such as:

  • Many drugs come onto the market without being thoroughly tested.
  • Drugs costing half a million or more may be no better than far cheaper ones.
  • Many drugs only increase survival by a few months.
  • Drugs known to be ineffective or dangerous may continue to be prescribed

Right on the first page, he makes no bones about the problem. ‘Our policies, our standards of evidence and our drug regulation,’ he writes ‘incentivise the pursuit of marginal or unproven therapies at lofty and unsustainable prices.’ We need a system focused on patients rather than profits.

Real game-changing drugs would make patients feel better

This is a long way from the optimistic, upbeat tone usually used to describe new cancer drugs. Calling them ‘game changers’ is common; with the expectation, they will transform patients’ chances.  

But most won’t work for over half of the patients. ‘Real game-changers,’ Dr Prasad claims, ‘would improve survival and make patients feel better.’. One analysis of 71 drugs licensed over more than a decade to 2014, found that, on average, patients got an extra 2.1 months. ‘The oncology profession owes it to patients to do better,’ he writes.

Dr Prasad’s aim is not to depress or frighten you but to let some light in on the complicated and specialist world of cancer treatments and show how the vast sums these drugs can earn is allowing inadequately tested and damaging drugs onto the market and what needs to be done to stop this. 

Although nearly all the research was done in America, the problems are very much the same in the UK. ‘The global research and development agenda revolves around what wins market share in America,’ says Dr Prasad. ‘The aim of a trial is to get a drug to market. The result is that it is hard for the UK and other countries to pay fair prices drugs.’ 

Drug trials done on younger fitter patients

He’s not claiming all the drugs are bad – one for cancer of the white blood cells (Imatinib), for example, allowed patients to live 27 years longer than they had on earlier treatments. But most improve survival time by far less. 

These drugs would nearly all have been tested in randomised controlled trials (RCTs), so how come they were licenced with such a small benefit? One reason is trials are too often done on patients who are younger and fitter than the people likely to get the disease.

While almost 60 per cent of cancer patients are 65 and older, just 33 per cent in the trials are that age. They also won’t have other conditions such as high blood pressure, suffered by these patients in the real world.

Just how damaging and disastrous a new but untested treatment can be, shows up horribly clearly in the case of ‘autologous stem cell transplant’ given mostly to women with breast cancer in the 1980’s. They got far higher doses of chemotherapy than normal to really blast the tumour. ‘Raise the dose as high as the patient can tolerate’ advised the director of the National Cancer Institute.

The ‘transplant’ element came because the toxic doses destroyed the ‘stem cells’ in bone-marrow that make new blood cells. The way around this serious side-effect was to remove some healthy stem cells before treatment and then inject them back when the chemo had been delivered.  It sounded plausible, if gruelling, but it took seven years for the results of several randomised trials to be published. 

Bad policy and bad evidence continue to harm people

Meanwhile, untested, it was given to over 40,000 women, earning over 120 million dollars for the main company providing the equipment. The trials found there was no benefit. 

 You might think this couldn’t happen today but Prasad’s point is that this disaster was possible because of the way the cancer drug industry works, which has barely changed, ‘Twenty years on,’ he writes ‘much of our system remains the same.  Bad policy and bad evidence continue to harm people who have cancer’. 

For instance, drugs are still being licensed, not on good evidence that they are effective, but because they achieve what is called ‘surrogate endpoints.’ In other words, changes in the tumour, such as shrinking, which seems a promising sign of improvement. The fact they do, however, does not mean patients are going to live any longer. Autologous stem cell transplant shrank tumours very impressively, for a while. 

Companies argue that using surrogate markers allow promising drugs to get onto the market much faster, and in return, they agree to keep track of how well they work and publish the data. But research shows that only half of these drugs are ever followed up, so information that could help to prescribe is lost. 

Research by Dr Prasad in 2015 showed just how unreliable surrogate markers can be. Just 14 per cent had let patients live longer – the result they most wanted from a drug.   

Large payments for doctors recommending cancer drugs

Another technique for boosting the use of new drugs is the enthusiastic endorsement by professors and consultants before the results of trials have come in. It worked for ‘autologous’ treatment and does for other ‘game changers’ today. What makes this practice worse is that many of those cheerleading experts are being paid large sums by the company making the drug.

But aren’t payments and promotions to doctors in the UK better controlled? ‘Medics get paid in all countries,’ replies Prasad. ‘The only difference is that in America payments are transparent. In the UK they aren’t.’ 

But it is not just high-profile consultants who have an interest in drug promotion. Official bodies produce guidelines recommending which drugs to use. One study of 125 guideline writers found that 84 per cent had received personal payments from companies. The average was 10,000 dollars but some got 100,000.

The eye-watering prices charged for cancer drugs contributes to the influence companies have over both the medical profession and the regulators. New drugs in the USA routinely cost 100,000 dollars a year but some are priced far higher – up to 800,000. 

The justification for these huge sums is that the R&D costs for one are extremely high – a commonly used figure is 2.6 billion dollars. However, Dr Prasad and his researchers ran a study on ten companies that have recently marketed new drugs using publicly available financial data and calculated that a more accurate cost would be 757 million.  

Drugs are priced simply on what the market will bear

But how exactly is the cost of cancer drugs calculated? If it wasn’t the result of R&D expense, perhaps it is linked to benefit to patients? Many surveys report that the most important result as far as patients are concerned is living longer.  So, Prasad and his team investigated. They found that wasn’t what drove up prices.

Drugs that shrank tumours (not a good guide to life extension) cost the most – 160,000 dollars a year. Those that increased survival cost, on average, 100,000 dollars. They also investigated whether drugs that worked better at what they were designed to do cost more. It didn’t.

Effectiveness made no difference to price either. In the end, the team concluded that: ‘Drugs are simply priced at what the market will bear. As a result, they cost too much and deliver too little.’

A common practice that makes this situation worse is known as ‘non-inferiority’ testing. It involves comparing a new drug with one already on the market. Not to show that the new one is better or safer but that it is ‘only’ no more than 30 or 40 per cent less effective.  

This might be done because it had some other benefits such as being cheaper or less toxic. Studies, however, have found that most come with no such benefits.

What needs to be done

Often no reason for doing the trial is given, yet nearly all meet the standard of ‘non-inferiority set by the company and so are licensed. ‘Another example,’ says Prasad ‘of policy favouring profits over patients.

The far-reaching changes needed to change the system include:

  • More trials that measure what is important to patients, such living longer than you would without the drug, and improving your quality of life. 
  • People in trials should match those likely to get cancer, rather than being younger and healthier. 
  • Allow patient advocates and experts with no commercial connections to be involved with licencing and treatment.  
  • Patient organisations should not be allowed to receive company funding. 
  • So, what can you or your friends or family do now? There is a whole chapter on how to use the information to ask your doctor some tough questions, such as: 
  • When a treatment is first suggested, ask ‘why that one?’ What is the data that supports it? What are the downsides? Why is it better than other ones? How toxic is it? Ask the same questions of any new treatment. 
  • Don’t rely on explanations based on what a drug does – unleashes the immune system – ask for the evidence it will do things you hope for, such as improve your life expectancy or quality of life. Ask if it was licenced based on surrogate markers or non-inferiority trials.

Given this charge sheet, the dogma that only the three official treatments – surgery, drugs and radiotherapy – can possibly benefit patients is clearly based more on faith than evidence. In fact, it’s time the standard model was humble enough to admit that it needs all the help it can get.

Jerome Burne

Jerome Burne

Jerome Burne is the editor of HealthInsightUK. He is an award-winning journalist who has been specialising in medicine and health for the last 10 years and now works mainly for the Daily Mail. His most recent book “The Hybrid Diet” was written with nutritionist Patrick Holford, published 2018. Award: 2015: Finalist for 'Blogger of the Year' Medical Journalists' Association.

1 Comment

  • Perhaps the whole idea of treating cancer needs to be reassessed. Certainly many people already have cancer, and everything possible should be done to extend their lives and – if possible – cure the disease.

    But consider that all the evidence gathered by doctors, scientists and other keen observers who visited “primitive” tribes untouched by the blessings of civilization shows that cancer was unknown to them. Not to mention all the other “diseases of civilization”.

    Obviously they were doing some things that we do not do, and not doing some things that we do. Eating and drinking healthily are obvious instances, along with adequate sleep, enough exercise, and less sustained (as in perpetual) stress.

    Factors like pollution are hard to deal with – especially as long as we have laws that encourage pollution and let “entrepreneurs” distribute their muck into the environment to poison us all.

    But isn’t it time more consideration was given to avoiding cancer, rather than healing it once it sets in? Rather as not knocking a priceless vase to the floor where it smashes into smithereens is much easier – and cheaper – than hiring an expert to try, painstakingly, to put it back together again.

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