It has been described as the beginning of the end of cancer. A new wave of drugs that harnesses the body’s immune system to destroy tumours is fuelling optimism that medical science is finally closing in on one of its greatest adversaries.
If that is true – and much is still to prove – it has been a very long beginning.
Medics have been experimenting with so-called immunotherapies for cancer since the 1850s. This was when German doctors noticed that tumours would sometimes shrink if they became infected and spurred an immune response from the patient.
Now, some 160 years and many false starts later, the principle of stimulating the body’s natural defences to fight cancer has finally found its moment.
Drug companies led by Merck and Bristol-Myers Squibb of the US are developing a range of treatments that aim to strip away the camouflage that cancer cells use to evade the immune system.
By unleashing the body’s disease-fighting T-cells against tumours, these drugs have shown the potential significantly to extend the lives of some people with advanced melanoma – the most deadly form of skin cancer – with work under way on therapies for several other tumours.
This expanding field of immuno-oncology will dominate discussion at the annual conference of the European Society for Medical Oncology starting in Madrid on Friday. The drugs are part of a broader revolution in our understanding and treatment of cancer, as advances in genomic science open the way to therapies that target the unique molecular and genetic characteristics of an individual’s cancer.
“Cancer treatment in the past has been as much art as science, with a lot of judgments made,” says Mike Standing, a life sciences specialist at Deloitte, the consultancy. “We are now moving towards precision treatments, where we have more meaningful understanding of what is driving a particular form of cancer.”
This progress has resulted in improved prospects for cancer patients – or at least those in rich countries where the latest drugs are available. One in 22 Americans – 14.5m people – are cancer survivors, defined as people who have lived for at least five years after diagnosis. This is triple the percentage seen 40 years ago, according to the American Association for Cancer Research.
Some commentators go so far as to say cancer could be about to experience a transformation similar to the one that has seen HIV downgraded from a death sentence to a manageable chronic disease when treated with antiretrovirals. Yet, just as science starts to catch up with cancer, the scale of the problem grows.
Already, 8.2m people die worldwide from cancer each year, according to the World Health Organisation. In the developed world, the disease accounts for about a quarter of deaths. These figures are expected to rise further in coming decades, as increasing longevity exposes more people to the biggest risk factor involved in cancer: old age.
“By 2020, almost half of Britain’s population will get cancer in their lifetime,” says Mr Standing.
Incidence is increasing in the developing world, in part because of high rates of smoking, which accounts for about a fifth of global cancer deaths. Other lifestyle factors associated with the disease, such as unhealthy diets and lack of exercise, are spreading beyond the west, as countries such as China and India become more industrialised.
All this threatens to increase the worldwide number of cancer cases by 57 per cent in the next 20 years, according to the WHO. This will impose a heavy burden on healthcare systems in developed and developing economies alike.
Global spending on cancer medicines reached $91bn last year, up from $37bn a decade ago, according to IMS Health, an industry research and data provider. By 2017, oncology spending in developed markets will be more than double that on the next most costly therapeutic area, diabetes, according to IMS forecasts.
This reflects the premium price commanded by cancer drugs – particularly in the US, where the average monthly cost of branded oncology medicines has doubled in the past decade to $10,000.
Cancer drug pricing is already a source of controversy in the US and Europe. These tensions will only intensify as incidence of the disease increases at the same time as new medicines keep patients alive longer.
“We are moving into a era where cancer becomes more of a chronic disease and that will require new economic models,” says Hilary Thomas, an oncologist and partner at KPMG.
Drugmakers says high prices are justified by high development costs. Cancer therapies account for more than 30 per cent of early-stage drug trials under way across the industry, but only a fraction of these reach market. Pharmaceutical companies say that, if the recent scientific momentum is to be sustained, they must make enough money on the successes to absorb the cost of the failures.
There is hope, however, that the same scientific advances that are leading to more effective drugs will eventually help bring costs under control. Increased understanding of the biology behind cancer should result in more selective treatments and more efficient clinical trials.
“There is nothing more expensive than a treatment that doesn’t work,” notes Peter Johnson, chief clinician at Cancer Research UK. “So, the key to making these drugs affordable is to make sure they are targeted at people who will benefit.”
The first big breakthroughs in targeted cancer medicine came more than a decade ago with the launch of Roche’s Herceptin for breast cancer and Novartis’ Glivec for leukaemia. Both have gone on to be blockbusters.
Today, targeted therapies account for 46 per cent of the cancer market, according to IMS.
These medicines attack specific proteins critical to cancer progression. This enables doctors to identify in advance the patients most likely to respond, based on expression of the targeted protein in their tumour.
Chris Boshoff, head of early development and translational oncology at Pfizer, says there is much to do.
The so-called checkpoint inhibitor drugs at the forefront of the immuno-oncology wave work by targeting proteins called PD-1 and PD-L1, but there are dozens more similar targets yet to be tested that could prove equally or more effective, he says.
Other approaches are being developed, including some involving the genetic re-engineering of patients’ T-cells to attack cancer. “If you get the target right, you can melt tumours,” says Paul Higham, chief executive of Immatics, a German immuno-oncology company.
“But if you get it wrong and it also goes after normal cells, then there is a huge risk of damaging healthy tissue. So, the key is to find the right targets that are over-expressed in cancer cells and under-represented in healthy cells.”
Some critics say there is too much focus on new drugs at the expense of spending on prevention, diagnostics and palliative care. For all the talk of a revolution in oncology, they say many new cancer drugs still only extend life by a few months not years.
Drugmakers argue that these incremental steps need reward because they will eventually arrive at a cure.
However, in an era of austerity and rising healthcare costs, companies are under increasing pressure to demonstrate that their therapies represent true innovation and value for money.