ASCO 2012: Is immunotherapy finally coming of age?

Delegates at this year's ASCO

While the UK enjoyed the rather wet Jubilee celebrations this weekend, thousands of cancer experts gathered in Chicago for the world’s largest annual cancer conference, ASCO. Cancer Research UK’s Nell Barrie was there to hear about the latest treatment advances.

In this first of her series of reports from the conference, Nell discusses one of the hot topics of the weekend – immunotherapy.

On a beautiful sunny Saturday in Chicago, hundreds of cancer researchers were packed into a stuffy, darkened room to hear the news that everyone had been talking about.

Last year the buzz at America’s biggest cancer treatment conference was all about immunotherapy – treatments that boost the power of the body’s own immune system. And once again a new drug designed to help the body in the fight against cancer was hitting the headlines.

With the last few stragglers trickling in and desperately trying to find seats, the presentations began – and we weren’t disappointed. An early-stage clinical trial of an experimental drug called BMS-936558 clearly showed its potential power.

When given to 76 patients with non–small-cell lung cancer, 14 of them responded (18 per cent), a figure which rose to 27 per cent among patients with kidney cancer (9 of 33 patients) and 28 per cent among patients with melanoma (26 of 94 patients responded).

Although these are preliminary results, they’re impressive. Until now, the best response rate researchers and doctors have seen for immunotherapy treatments is a little more than 1 in 10 (10 per cent).

And to add to the buzz, it’s the first time immunotherapy has been shown to have a real benefit for lung cancer patients – people desperately in need of better treatments.

Treating the immune system

So how does the drug work? One speaker put his finger on it when he explained that this new approach is “treating the immune system, not the cancer” – and this turns out to be the secret of its success so far.

Researchers have known for years that cancer cells are very good at evading the body’s natural defence mechanisms. It seems that our bodies’ immune systems can’t spot cancer cells and eliminate them, in the way they do for bacteria and viruses. Cancer cells are very good at finding ways to survive, and one way they do this is by interacting with immune cells to tell them (in cell signalling language) to back off.

One way they do this is by mounting a protein called PDL1 on their outer surfaces as a way to protect themselves against T cells, the soldiers of the immune system. PDL1 sticks to a protein partner found on the surface of the T cells, called PD1. This interaction tells the T cells to stop attacking – they go into shutdown, like “a car without gas”, as one conference speaker put it. This process is actually part of a clever failsafe that’s meant to protect the body’s own cells against T-cells – the cancer cells have co-opted this defence for their own ends.

This ingenious strategy works very well for the cancer cells, but now researchers have found a way to turn the T cells back on. The new antibody drug targets PD1, literally stepping in and blocking the cancer cells’ defence by preventing PD1 and PDL1 from sticking together.

This means the T cells can do the job they’re meant for – recognising a threat to the body and eliminating it. And, excitingly, it could mean that this new treatment may have long term effects. One key aspect of the immune system is its memory – once it’s recognised a problem, it doesn’t forget.

Researchers hope that by giving the T cells a chance to engage the enemy, they could also be ensuring that the immune system will recognise the cancer cells for months and maybe years to come. With a few patients showing long term benefits, hopes are high.

But as with any breaking news on a brand new drug, it’s still early days. The trial that’s just been published only tested the drug in 296 patients, and we don’t yet know the long-term effects of treatment. We’ll need larger studies to be sure of the potential benefits.

Need for caution

The need for caution was emphasised by reports of some of the side effects. For all their promise, immunotherapies can sometimes cause some serious problems because of the way they interfere with the immune system. Boosting the immune response against cancer can mean the immune cells start to attack healthy tissues too, causing symptoms like skin rashes and diarrhoea.

It was upsetting to hear that three patients on the trial had died because of severe reactions that affected their lungs. The researchers in charge quickly found ways to identify patients most likely to have problems, and to treat the early signs of dangerous side effects. But the lesson is clear: all drugs have risks.

On the other hand, there are hopes that anti-PD1 drugs could be less dangerous than some other immunotherapies. The protein that the drug targets is only made by cells in areas where there is already inflammation – so the drug should have very little effect in healthy tissues.

And the drug’s ability to home in on this protein could also help researchers identify which patients could benefit most from treatment. It’s possible to measure levels of PDL1 in and around a tumour – evidence so far suggests that patients with higher levels are more likely to show a good response to the drug. This is a vital clue – a new targeted drug can only help specific groups of patients if researchers and doctors have a way to find those people, and these results are one step towards that goal.

Suppressed excitement

Overall, the mood at the end of the session was one of suppressed excitement. The researchers who were in the room know only too well how complex a problem cancer is – new treatments fall by the wayside every day. But they also know that few immunotherapy treatments have ever looked this promising.

It was especially moving to hear one melanoma expert joyfully saying that he had never expected to see such progress against this type of cancer in his lifetime. Anti-PD1 drugs, together with the melanoma treatments feted at last year’s ASCO conference, represent a huge leap forward in treating this dangerous form of skin cancer.

And because anti-PD1 drugs target the immune system and not specific cancer cells, they could potentially be used to treat many other cancers too – an exciting prospect in this era of highly specialised drugs.

As the editorial in the New England Journal of Medicine concludes, drugs like this “may well have a major effect on cancer treatment”.

With new trials already under way, we’ll know much more in the months and years to come.

Reference

Topalian SL et al. (2012). Safety, Activity, and Immune Correlates of Anti-PD-1 Antibody in Cancer. The New England Journal of Medicine PMID: 22658127