ASCO 2013

ASCO 2013 highlights

Dr Gary K. Schwartz - Memorial Sloan-Kettering Cancer Center, New York, USA

So the highlights to me, if we talk about the big results of the meeting, it would have to be in melanoma. This is the year, again, we transform melanoma. It started two years ago when we identified new genes or proteins that were abnormal in melanoma with a gene called B-Raf. This is mutated 50% of the time in patients with melanoma and we saw the first results of a drug called vemurafenib, a B-Raf inhibitor, for which we saw unbelievable activity which ultimately in clinical trials prolonged survival for the first time patient with metastatic melanoma.

The same time two years ago we saw the first results of a drug called ipilimumab, a drug that activates immunity. And this drug also two years ago showed for the first time prolongation of survival with a drug that activates the immune system. At this year’s meeting we see two new drugs and advances further with PD1, another drug that activates immunity. Now some of this data was presented at ASCO last year, this year we saw the update showing again the amazing activity and how this also prolongs survival. However, now we see the combination of PD1 with the former drug ipilimumab and now we see unbelievable clinical activity with survival of 85% at one year for patients with metastatic melanoma, unheard of in medical oncology, with response rates that exceed anything we would have expected with either ipilimumab by itself, PD1 by itself or even better, or at least as good as, the prior drug vemurafenib to target a small molecule. So this represents a major advance in medical oncology, an advance that will change the whole field for patients with this horrible disease.

In addition there’s another major clinical trial with a very rare form of cancer called ocular melanoma or uveal melanoma. It’s different than regular melanoma, they have a different mutation, it’s called GNAQ and activates other pathways that are druggable. One of the pathways is called MAP kinase. So at this meeting we saw the first randomised study of a MAP kinase inhibitor called selumetinib, or AZD6244, versus chemotherapy – temozolomide. This is based on laboratory data showing that this drug is highly effective against this particular tumour cell. This represents the first clinical trial evaluating that drug and for the first time in oncology we have a drug that shows a clinical benefit for patients with metastatic ocular melanoma to the liver, a horrible cancer for which there are no effective therapies. And for the first time in medical oncology we have a drug which shows promise and benefit for patients with this disease. This represents a huge breakthrough for a very rare cancer for which no effective therapies previously existed. This is a global effect; this is a drug that affects people all over the world and, I think, represents a major step forward in cancer therapeutics for patients in the history of medical oncology.

To me this represents in melanoma a series of outstanding breakthroughs. ASCO makes it possible to present this data. This is based on international collaborations by investigators from the United States and Europe and other parts of the world to make it possible to treat patients with metastatic melanoma, to make sure we have new cures for patients with these horrible diseases.

Do you think melanoma drugs will also be used for other diseases in the future?

Absolutely, so we’re seeing these results now in renal cancer, lung cancer and other diseases, especially immune activation. For years we wondered, why doesn’t immunity kill cancer cells? As a medical oncologist at Memorial Sloan-Kettering Cancer Center I used to get that question asked me all the time – ‘Why doesn’t my immune system kill the cancer cells, Dr Schwartz? What can I take medically, what foods can I eat to build up my immunity?’ Well the problem is by evolution our immune system has been turned off. The reason for this is because if our immune system was turned on it would not only kill cancer cells, it would attack every cell of our body. And there are actually conditions, medical conditions, where immunity is active all the time, one of them is called lupus, ulcerative colitis, other connective tissue diseases in which patients die of immune activation of their system. So by evolution our immune system is turned off; the question is can we turn it on? And that’s what we’ve now found with ipilimumab and now PD1, nivolumab, to show that we can activate the immunity. These aren’t systems unique to melanoma, immune suppression is everybody in the whole world walks around with this problem. It’s not a problem, it’s protecting our bodies from an overactive immune system. Now we find ways to turn on immunity; with ipilimumab we have the first turning on. The problem with that drug is toxicity, we’ve had a lot of side effects so we can now manage them but it reflects the fact that when you turn on immunity not only does immunity turn against the cancer cell, it can also turn against the body. We get diarrhoea, we get effects on the heart, the liver etc. With PD1 it’s more specific for the tumour cell and now we have less toxicity, more specific immune activation against the cancer cell and not against the host. So now we have a big advance with less side effects, more tumour specificity, we think, and ways to combine them with the older drug to cause even greater anti-tumour effects with effects that were impossible before just with ipilimumab alone or with PD1 by itself.

So that’s the advance and this advance will be extended to all tumour types. There’s no reason to think it won’t be because, frankly, immune suppression is part of our body, part of our biology, it’s how we evolved, for better or for worse. Now we can turn it on but turn it on specifically for the tumour. And melanoma is one way to do it and why shouldn’t it work in renal cancer, lung cancer, hepatoma, sarcomas, breast cancer? It’s all being tested. This is the future and we’re going to see great advances across oncology in multiple solid tumours for the next two to three years. It’s happening now.