7:30PM BST 07 Jun 2014
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Some have been bold enough to call it a cure for cancer. Those of a more conservative bent point to early signs of dramatically extended survival. But whoever you ask, an experimental treatment known as immuno-oncology (IO) is the most exciting development in cancer care for years.
A small mountain of evidence is building for this once marginal area of cancer research. Nowhere was this clearer than at the annual jamboree for the great and good in cancer care, the American Society of Clinical Oncology (Asco), where attendees last week were bowled over by a wealth of promising clinical trial results.
IO is set apart from other forms of cancer treatment because it harnesses the body’s natural defences to fight off tumours. The other approaches – chemotherapy, radiotherapy and surgery – bring in outside weapons, such as powerful drugs, high-energy radiation and scalpels.
IO works by undermining the evasion tactics used by tumours, which can “hide” from the body’s immune system by disguising themselves as normal cells. Some IO treatments work by unmasking tumours, allowing the body’s disease-fighting cells to find and attack them. Others reinforce the immune system’s weaponry in various ways, so that its killer cells can fight off the cancer more powerfully.
David Hafler has spent decades, first at Harvard University and now at Yale, working out how scientists can harness the immune system to fight off disease of all kinds, not just cancer. “The word breakthrough should be taken very seriously, but this is one of just two instances in my life when I would say: this is a breakthrough,” he says.
He calls some of the trial results “mind-blowing”, especially in the treatments that attack a tumour’s stealth tactics. “It’s been absolutely dramatic to watch play out. The cat-and-mouse game that goes on between tumours and the immune system – I didn’t know it was that important. No-one did.”
Dr Roy Baynes, senior vice-president of clinical research at Merck, says he believes the field is going through a “watershed” moment. “The volume of material [on IO at Asco] this year was almost unprecedented,” he says.
The idea of using immunotherapy against cancer first emerged in the early Nineties, but the present generation of treatments only surfaced in the past few years.
Bristol-Myers Squibb (BMS) is so far the only company to get a drug of this type approved, but many of the world’s major drug-makers have joined the race for a slice of a market thought to be worth tens of billions of dollars a year.
Other companies are hopeful that newer drugs, targeting a different part of the cancer “stealth cloak”, might prove less risky than BMS’s drug, known as Yervoy, which has some serious side effects. BMS also has alternative drugs in its pipeline.
The eventual size of the IO market hangs on two crucial factors: by how much it can increase survival and how many types of cancer it can work on. Last week’s meeting of Asco showed promise on both fronts.
Several drug-makers unveiled early data showing dramatic improvements when IO was used in combination with other drugs.
BMS said 79pc of the 53 melanoma patients treated with a combination of Yervoy and another immunotherapy survived for at least two years.
AstraZeneca plans to launch clinical trials testing various combinations of its most advanced IO drug with its other cancer medicines later this year.
There was also a wave of trial results suggesting that IO could be used to treat tumours in the bladder, head and neck. If scientists can build on this evidence, it would mark a significant expansion of the potential for the treatment, which has so far focused on melanoma and kidney cancer.
The Swiss drug giant Roche provided the first evidence that IO could work in advanced bladder cancer. Its experimental treatment shrank tumours in 13 of the 30 patients in the trial. The tumours completely disappeared in two patients.
“This is by far the most exciting treatment that I’ve tested on bladder cancer,” said Dr Thomas Powles, a medical oncologist at Barts Hospital in London, who led the clinical trial. “It worked much faster than we expected and much more dramatically.”
Merck showed off data on its leading immunotherapy treatment, from trials on advanced head and neck cancer, in which 11 of the 56 patients responded to the treatment.
But most exciting of all are signs that immunotherapy could work in lung cancer, the biggest killer of all with an annual death toll of 1.5m.
Roche has already started a large-scale clinical trial on lung patients using the same drug that has shown promise in bladder cancer.
Merck and Bristol-Myers Squibb are also leading the charge on this front.
The pair of US companies both unveiled data at Asco showing that their respective “checkpoint inhibitor” drugs had an effect on lung cancer.
Merck’s MK-3475 treatment shrank tumours in 28 of the 35 patients on which it tested the drug.
BMS also demonstrated that its drug, nivolumab, might work in lung cancer. The best results were in 20 patients known to have a particular type of cancer cell, half of whom responded to the treatment.
AstraZeneca is not far behind. Its experimental immunotherapy, known as MEDI4736, produced such promising results in lung cancer patients that it was fast-tracked to late-stage testing only 18 months after the first tests in humans.
Justin Stebbing, professor of cancer medicine at Imperial College London, is running clinical trials using IO on patients with lung cancer and says the results look “really hopeful” already. “If we can take some of those patients and induce long term remission, that will change everything,” he said.
“The [old] idea of where immunotherapy might work has been shattered,” added Michael Giordano, head of oncology at BMS. Its Yervoy, which at present is only approved for use in so-called metastatic melanoma, is a case in point. BMS presented a string of data at Asco indicating that the drug could help to beat off a return of melanoma after it has been surgically removed.
The drug-maker is also testing out nivolumab on patients with kidney, blood, breast, gastric, brain, colorectal and pancreatic cancers.
Big Pharma has largely focused on the stealth-cloak busting approach, but drug-makers are exploring other approaches too. Novartis is developing a treatment which involves taking blood out of a patient and re-programming the “killer cells”, or T-cells, to make them even more powerful.
It has tested this approach in approximately 40 patients with a deadly blood cancer known as acute lymphoblastic leukaemia and found that tumours completely disappeared in 80pc of cases.
Alessandro Riva, head of oncology development at Novartis, says this kind of response had never before been seen in this disease.
“It’s like creating an armed robot,” said Paul Highams, chief executive of immatics – a private German company working in IO. “Natural T-cells are good but you can enhance them by putting more weapons on them”.
Immatics’ specialty is cancer vaccines which is a related branch of IO.
The way these treatments work is to train the body’s immune system to recognise the subtle differences between cancer cells and normal cells that it might not otherwise pick up on.
The company is in the advanced stages of developing a vaccine for kidney cancer and has several more candidates in the pipeline.
Last year, it signed a deal with Roche in which the Swiss drug giant will take on the development of some of immatics’ early stage research and develop new joint products.
Scancell, a company spun out of Nottingham University in 1997, is also developing cancer vaccines.
Cancer immunotherapy has the potential to create many winners among drug companies big and small – Andrew Baum at Citi believes the market could swell to $35bn (£21bn) annually, and that IO will play a part in at least 60pc of cancer cases.
But whoever emerges among the leading pharmaceutical players, one thing seems almost certain: patients will start benefiting hugely from these advances.
Prof Hafler says that, in melanoma at least, there is “no question these drugs now provide the hope to patients for disease-free remission”.
Dr Powles is also hopeful. “At times the oncology community can get over-excited. But this does look like some of that optimism is justified.”
