Precision medicine the theme at world’s biggest cancer conference
New era of targeted treatment that will extend survival rates detailed at American Society of Clinical Oncology meeting
A new era of cancer treatment is beginning in which patients get drugs matched specifically to their tumour, according to scientists at the world’s biggest cancer conference in Chicago.
Precision or personalised medicine, as it is called, “is about targeting treatment so that it’s more powerful, while reducing the toxicity, so there are fewer side-effects”, said Prof Roy Herbst, chief of medical oncology at Yale Cancer Center. “At the moment it’s more like using a cannonball to kill an ant – and creating a whole lot of damage at the same time.”
The talk at the American Society of Clinical Oncology (Asco) annual meeting this weekend is of longer survival and fewer toxic effects through this approach, which is being made possible by advances in genetic profiling of the tumour itself.
A number of studies will present results at Asco showing that this approach can extend survival in many different cancer types, while a study being launched in the UK – if all goes as experts hope – could result in up to 7,000 women being spared the toxic side-effects of chemotherapy, while saving the NHS an estimated £17m.
The UK trial, called Optima, is being run by University College London and Cambridge University and funded by Cancer Research UK. Beginning in the summer, it will recruit 4,500 women with breast cancer, whose tumours will be genetically tested as soon as they are diagnosed to establish which will respond to chemotherapy and which will not.
“It will be a significant step forward,” said Dr Robert Stein, a consultant in breast cancer at UCL. “In every area of cancer treatment we have largely functioned on a one-size-fits-all basis because we didn’t have tools to do any better.”
Of the 50,000 or so women diagnosed with breast cancer in the UK each year, about 40%, or 20,000, are currently given chemotherapy but only half of them do well as a result of it; in the other half, the benefit is unclear. The researchers hope to find out which of the latter group actually need chemotherapy.
“We would expect to reduce chemotherapy within the trial population by about two-thirds,” said Stein. “We are looking at between 5,500 and 7,000 fewer a year being treated with chemotherapy than are currently treated. It’s quite a big deal.”
The downside of chemotherapy is serious. “There are a small proportion of women who die from treatment. I normally quote 1%,” said Stein. People can be off work for six months to one year and some never recover emotionally, he said.
Precision medicine, one of the main themes at Asco this year, was described by Herbst as “about finding the right key for the lock – finding out what it is that is driving the tumour, what makes it tick. At the moment it is informed guesswork, so that treatment often doesn’t work for large numbers of patients.
“In some ways it is simple – it means that you can make sure you are giving the right drug to the right person at the right time. In others it is very complex, because there are so many pieces to the jigsaw. We need to put the puzzle together.”
The future is already here, said Herbst. Patients who are given the more established “targeted therapies”, the best known of which is Herceptin, are already tested to ensure they are among the group in the population whose tumour has a particular genetic variation.
Herceptin works only for the 20-25% of women whose breast cancer is Her2 positive – it has too much of a protein called human epidermal growth factor receptor 2, which makes the tumour grow.
About half of melanomas have a mutation in a gene called BRAF. Drugs targeting BRAF have had some spectacular, if sometimes short-lived, results but can be dangerous in people whose tumours do not have the mutation.
Instead of these single tests to match a patient with a specific drug, many experts want to see genetic profiling of all tumours, in the hope that they can design a package of treatment to suit the individual. But cost is an issue.
“I think in five years’ time we will be profiling most patients,” said Herbst, who is leading a trial on personalised medicine in 800 patients with advanced squamous cell lung cancer called the Lung Cancer Master Protocol (Lung-MAP) and is an honorary professor at UCL. “The difficulty is resources – this is $4,000 to $5,000 per test,” he said. “I think they [the NHS] need to find a way to fund it.”
Genetic testing can be used to select the patients who will best respond even in early clinical trials of new drugs, a study presented at Asco has found. These trials are mainly intended to establish whether the drug is safe, but the study of more than 13,000 patients in 346 trials found that patients had significantly better outcomes where genetic profiling took place.
In trials using precision medicine, tumour shrinkage rates were 30.6% compared with only 4.9% in those that did not.
Maria Schwaederle, of the Center for Personalized Cancer Therapy at the University of California San Diego school of medicine, said: “Our study suggests that, with a precision medicine approach, we can use a patient’s individual tumour biomarkers to determine whether they are likely to benefit from a particular therapy, even when that therapy is at the earliest stage of clinical development.”