There are plenty of advances in oncology treatments to be excited about – from immunotherapy to cancer vaccines and monoclonal antibodies – but unfortunately cancer is such a complex disease that none of these are guaranteed to work for every patient.
Precision medicine may be the answer to this problem. Also known as personalised medicine, it involves giving patients the treatments that will best help their condition based on specific genetic biomarkers they display.
Through advanced diagnostic tests, precise differences in patient’s genes can be taken into account when examining their illness, and then a drug that suits these factors can be prescribed.
This sounds and is a simple concept, but it is a genuine departure from standard treatments like chemotherapy, which take a one-size-fits-all approach that can be successful for some patients but not for others.
In cancer, this means discovering the specific genetic abnormalities of a patient’s tumour, and prescribing the drugs that will work best against that exact kind of cancer.
In oncology precision medicine is not just a hope for the future, though – the methodology around it is being used to develop drugs right now. This is particularly true for lung cancer, where some of the biggest strides in precision medicine have been made, thanks in part to the large amount of molecular profiling being done in the area.
“Lung cancer has been leading the way currently in the advances in the field of personalised treatment,” says Professor Rolf Stahel, president of the European Society for Medical Oncology (ESMO) and a member of the International Association for the Study of Lung Cancer. “Now the most enthusiasm is really in that field – along with melanoma.”
Kevin Loth is executive director of corporate affairs and policy, EMEA, at Celgene – manufacturers of the melanoma drug Revlimid (lenalidomide), which also targets a genetic biomarker called the 5q deletion in people with a cancer called myelodysplastic syndrome.
He says: “Truly personalised treatment is the holy grail in all therapy areas. Being able to predict a positive patient outcome before prescribing a particular medication saves valuable time and resources and is in everyone’s best interest”. Although he admits: “In some diseases we are closer to this goal than others.”
Other types of cancer are seeing advances in precision treatment too. A recent study of Janssen’s Zytiga (abiraterone) suggested that it is possible to identify a subgroup of men with very aggressive prostate cancer and changes to a gene called ERG who may benefit particularly well from taking the drug before chemotherapy.
Developing precision drugs
The need for a biomarker in order to know which precision treatment to prescribe means that diagnostics and targeted drugs are often developed together.
Dr Rob Sands, senior medical director of EMEA oncology at Astellas, gives some insight into how this development process might go: “With a lot of these biomarkers it’s all very hypothetical and it’s at the prognostics stage, it hasn’t been validated as a predictive biomarker, and that is important work that needs to be done. Once it’s been established that a biomarker is indeed predictive, that it’s accurate and it’s sensitive so you’re not going to mislabel patients as having a disease when they don’t, then it can be incorporated in the development programme.
“You identify patients in Phase II studies, and the inclusion criteria state that these patients have to have this biomarker present. You have special designs and statistical plans around that which then lead to the approval of both your drug and your biomarker, so that the regulatory bodies see this as a package of treatment. I think that’s the ideal, and there are some examples where this has happened, so it can be done.”
Benefits, challenges and risks
Precision medicine has huge expectations from the life sciences community resting on its shoulders – as researchers at the University of Birmingham put it: “It is widely recognised as the new way to deliver healthcare”.
“You have a faster, better response to targeted treatment,” says Stahel. “The side effects are different though – I don’t say there are none – and you have a longer life.”
Stahel was a panellist at the 2015 Astellas Innovation Debate on personalised medicine in January. He discussed the future of the area with gene sequencing pioneer Dr Leroy Hood, who describes himself as “amazed at how dominant a role genomic medicine plays in most people’s thinking about the future of medicine”.
Despite disagreement on finer points such as genetic screening at birth and the use of genetic data for more mundane health recommendations, all the panellists and many members of the audience seemed confident that precision medicine would be able to live up to its potential.
Governments are beginning to throw their weight behind it too. The UK’s innovation agency, Innovate UK, is setting up a centre for precision medicine, with the aim of “making the country the leading place worldwide to develop and launch new solutions in this space”.
And in the US, President Barack Obama said in January’s State of the Union address that he wanted the country to “lead a new era of medicine – one that delivers the right treatment at the right time” and brings them “closer to curing diseases like cancer and diabetes”.
The US government is now looking to invest $215 million in the area. Some $130 million of this will go to the National Institutes for Health to establish a cohort of over a million volunteers to help further advance the understanding of health and disease, and $70 million will go to the National Cancer Institute to help identify genomic drivers in cancer to develop more effective treatments.
The FDA will get $10 million towards building a regulatory structure that can facilitate innovation in precision medicine, which will include acquiring additional expertise and developing genetic databases.
Despite the enthusiasm from the UK and US governments, precision medicine is not completely free of risks and challenges, however.
“The challenges are how do you get it predictive?” Ken Jones, Astellas Europe’s chief executive says. “How do you get it where it’s standardised, where you can do it on a mass scale and ensure you’re not misdiagnosing people?
“That’s where the rigour of development, and the rigour of the process of Phase II to Phase III and IV has become really important – as has making sure ethically and morally it’s accessible to the right patients in the right manner, preventing misuse or misdiagnosis. So there’s a whole wider context.”
That context, Jones says, is about the credibility of the technology and the accuracy of the treatment.
“You could be increasing the worried well, or it actually might not be relevant and you’d be contributing to wastage. So you need to make sure that the diagnostics and the guidelines are very clear about what treatments should be done, when you should use the biomarkers and when you should not.”
One of the concerns Stahel has is how best to provide the right access to the technology.
“The problem is, do patients have access to the diagnostic, does the doctor give the patients access, and if he gets the data is the patient referred to a centre where its staff knows what to do? So the access I think, it’s not a danger, but it’s a hurdle.”
Jones adds: “I think you need to walk before you run. If everyone runs ahead too fast I think some of the concerns may be realised. That’s why it needs to be done responsibly.
“It needs to be done within a framework and using science where the smart technologies, the research, development and so on, really have a high propensity of giving credibility and accuracy.”
Costs and regulation
Another concern might be the availability of precision treatment. With so many heated debates about costs and market access surrounding organisations like NICE and the NHS in the UK, how difficult will it be for them to adapt to potentially assessing, regulating and buying different cancer treatments for all kinds of genetic variations?
“[Regulators] will need new rules,” Stahel says. “Because the genetic changes are rare, you cannot do, like the old days, large clinical trials of 1,000 patients. So there need to be new trials, which really identify patients with a high likelihood of having a response.
“The EMA is now thinking in these terms, so they’re really moving to welcome the new way to do this. We’re in discussions between ESMO and the EMA on rare cancers, and how medical trials can be done in the future.”
Rob Sands, meanwhile, thinks that the issue of cost may not be as problematic as it first seems: “Although the actual technology and medicine cost more there’s less wastage, so overall the health providers benefit, the patients benefit and pharma benefits. So there’s a win-win across the board.”
Working with immunotherapy
What Stahel is most excited about is the combination of precision medicine and another exciting new treatment type in cancer – immunotherapy, which uses the body’s own immune system to fight against the disease.
“We do personalised medicine, oncogenic drivers, targeted treatments, and now comes the immune checkpoint inhibitors which provide a revolution in the treatment of cancer. So, I’m quite excited about that.
“I have to say there’s going to be a total shift to personalised treatment and immunotherapy away from standard treatments. Genomics will not replace [immunotherapy]. When something good works, we use it all.”
While Stahel says that he thinks this shift will happen within the next 10 to15 years, he also cautions that there is not yet enough data to say for certain how genetics and immunotherapy will complement each other.
“There are some people who think those rare cancers that have an oncogenic driver mutation may have less genetic changes in the cancer, and may be less susceptible to immunotherapy, but we don’t know for sure yet.”
It’s important to keep in mind that precision medicine does not have to mean completely new kinds of drugs – it can easily work with existing treatments too. This means it is less of a treatment revolution and more an inevitable shift in the way cancer is fundamentally approached.
The enthusiasm about precision medicines seems justified when considered in the terms Jones puts it. “We’re now at the cusp, the beginning of a new journey with technology and science coming together, where these possibilities are going to become more prevalent than in the past.”
Though there are plenty of questions still to answer, from this perspective the unusually robust optimism coming from pharma firms, governments and researchers alike does indeed seem merited.