ASCO 2016: will fine-tuning treatments require redefined tumours?

Breast cancer, bowel cancer, lung cancer: different diseases, each intimately tied to the location in the body where they reside.

Defining tumours in this way makes sense. These tissues and organs may be where a patient first finds a lump, or where the signs of a tumour appear on a scan. They also form the foundations of how surgeons specialise, and on which many clinical trials are built.

But as scientists develop greater precision in how they pick apart the molecular details of tumours, the lines between these definitions are steadily beginning to fragment – or in some cases blur.

The term ‘breast cancer’ now spans 10 different diseases, thanks to landmark work from our scientists. Just last week, UK researchers uncovered how one type of blood cancer was actually 11. And entire clinical trials are now being planned based on the genetic faults fuelling a tumour’s growth, rather than where it sits in the body.

This doesn’t necessarily mean the end of body-based tumour classification – but it could prove pivotal in the drive to personalise treatment. And giving scientists access to vast amounts of data could have a key role to play too.

These were the take home messages from the annual mass-gathering of the great and the good in cancer: the American Society of Clinical Oncology (ASCO) conference, which took place in Chicago last week.

In discussions of the latest targeted treatments and immunotherapies, the focus was on picking apart the fundamental biology of each patient’s cancer. And by doing so, many scientists and doctors are confident that, for some cancers at least, precision treatment may be just around the corner.

Getting personal

The idea of tailoring treatment based on the underlying genetics of a tumour isn’t new. So-called targeted treatments take aim at key molecules inside or on the surface of tumour cells, killing those cells that carry them.

This can lead to profound responses in patients whose tumours rely of these molecules to grow. But in many cases, patients will also see the disease return as the tumour develops new ways to grow and outsmart these drugs.

Aside from this, the key point raised by several presentations at the conference was that these faulty genes and molecules aren’t confined to particular types of cancer. The same gene fault found in more than half of melanomas also turns up in a proportion of bowel cancers, for example.

And as we reported from the conference, early-stage trials looking to find commonalities between tumours from different organs or tissues – and, crucially, match this to an available targeted drug – are showing some promise.

The UK media homed in on this precision approach. And our chief clinician, Professor Peter Johnson, described this as a move from treatments chosen on the basis of where the cancer starts and what it looks like, “to an era of molecular-designed therapy, targeting a tumour’s genetic fingerprint”.

But it’s still early days. And larger clinical trials specifically designed to test this approach are still needed before any true benefit becomes clear.

ASCO itself has committed to the approach, launching its first ever clinical trial matching drugs with genetic faults – called TAPUR – last year, with an update at this year’s conference.

And our own National Lung Matrix trial is matching a raft of different targeted drugs to patients with lung cancer based on their tumour’s genetic fingerprint.

For many, including the mainstream media, it may seem that this is where the personalised medicine story ends for ASCO this year. But that really wasn’t the case.

Immunotherapy is here, but what next?

If you’ve an eye on the latest developments in cancer then it’ll be no surprise to hear that, once again, immunotherapy featured as one of the headliners at ASCO, and we heard how the list of tumours that may be susceptible to drugs that harness the body’s immune system is growing.

But following last year’s headlines hailing ‘revolutionary’ therapies that were the ‘biggest breakthrough since chemotherapy’, the focus this year was very much about the nitty gritty of understanding how these treatments actually work.

Crucially, this means that the need to tailor treatment isn’t limited to targeted drugs. When immunotherapy works, while patients may see long term responses (at least based on what we’ve seen for advanced melanomas and some lung cancers), they don’t work for everyone.

The challenge now, and the focus of several talks at the conference, is understanding why – with the ultimate goals being to make the drugs effective for more patients, or tailoring a chosen immunotherapy for each patient.

As we reported, scientists are sifting through genetic data from tumours that respond and those that don’t. And promising early results suggest that bladder and bowel tumours carrying DNA littered with faults may be more likely to respond to immunotherapy drugs. But these studies are still in their early stages, so longer term follow-up involving many more patients will be needed before a clear consensus emerges.

As well as revealing the potential of profiling a tumour’s DNA to predict who will benefit, other studies showed how combining different immunotherapy drugs could also reap rewards.

As we reported from the conference, two trials, testing combinations of immunotherapy drugs in different types of lung cancer, showed early promise. The combined treatment doubled the number of patients who saw their tumour stop growing, compared to a single drug.

The challenge here though is side effects, which were much more severe for the combination treatment. But many experts agreed that combination treatments mark the next step for immunotherapy.

Our chief clinician told the Mail Online that the combination approach could lead to responses in patients where the single treatment approach hasn’t worked.

But Dr Jedd Wolchock, from the Memorial Sloan Kettering Cancer Center in New York, cautioned during a high-profile immunotherapy session that the approach “is going to take some tinkering before we know what will work for each patient”.

Open mind set, open data set

One thing all these trials and studies share is that they involved analysis of large amounts of data. What to do with this data, and the billions of bytes that will follow in the coming years, was the focus of US Vice President Joe Biden’s speech to the conference.

As with the recent American Association for Cancer Research (AACR) conference in April, Biden – who lost his son to a brain tumour just a few years ago – was in attendance to stir enthusiasm for his cancer ‘moonshot’ initiative. And at ASCO, he announced the latest part of his plan: The Genomic Data Commons – a vast database of genetic data from as many tumour samples as possible

The database will launch with data drawn from several large-scale studies already in the public domain, but Biden said that from now on, all patients enrolled in trials funded by the US National Cancer Institute will see their data fed into the system.

“I want to assure you it’s built with safeguards,” he said, in reference to keeping the data anonymous. But the database’s key feature will be that it’s freely accessible to researchers so they can analyse the data how they wish. And he hopes that those researchers who benefit will share data from their studies too.

This, Biden said, was key to finding patterns in cancer’s genetic life-story that could point to new ways to personalise treatment.

Oncologists have to explore the unknown with their patients, he told the audience. “The unknown is frightening, I know from experience. My family and I did everything in our power to learn everything about the cancer that my son was fighting,” he added.

His hope is that, by pulling together then opening up these vast quantities of data – and getting scientists to share – those unknowns will more quickly become known.

Nick