Comment: Immunotherapy combo increases median survival in advanced melanoma

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Published: 2 Jun 2014
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Dr Steven O'Day - Beverly Hills Cancer Center, Los Angeles, USA

At ASCO 2014, Dr O'Day provides ecancertv with his expert opinion on the results from an expanded phase I study which showed that concurrent treatment with immunotherapy drugs ipilimumab and nivolumab produces an increased median survival of roughly three and a half years (40 months) for patients with advanced melanoma. 

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ecancer's filming at ASCO has been kindly supported by Amgen through the ECMS Foundation. ecancer is editorially independent and there is no influence over content.

We have ipilimumab, the first checkpoint inhibitor, that shows benefit in about one in four patients; we have PD1 that seems to be benefiting up to two-thirds, they’re not necessarily overlapping, and now we’ve combined these two drugs in about 53 patients and he updated that from last year.

So that’s nivolumab and ipilimumab together?


What do you make of Dr Sznol’s results then?

They are obviously very exciting because he’s reporting two year survival rates of almost 80% which is historic in melanoma. But when you really compare the combination in this small group of patients to the PD1 data that was presented by Dr Rebus in terms of the clinical benefit and the response rates they’re quite comparable. The real differentiating is going to be do they lead to better survival at two and three years. Right now, preliminarily, the combination does look superior but they haven’t been compared and we need larger numbers.

Now this is in advanced melanoma but do you choose your patients?

No, that’s the beauty of these checkpoint inhibitors, unlike previous immunotherapy like with high dose IL2 where we select patients with more modest disease and younger patients, it doesn’t appear that age, sites of disease and many other factors are critical to the immune response. As long as they’re not so sick from the cancer that they don’t have time.

What’s your feeling about the way checkpoint inhibition in melanoma is going and the scope for multiple checkpoint inhibition?

I think it’s going to set the new platform for melanoma and in the next ten years we’re going to be producing long-term survival in the majority of our patients. But its real beauty, I think, right now is it’s so successful in melanoma that it’s bursting out of its disease into other solid tumours and we’re seeing at this conference the significant impact it could potentially have on other solid tumours.

But with these powerful therapies is toxicity an issue?

Yes, absolutely. With ipilimumab as well as the PD1, the checkpoint inhibitors, when you activate T-cells to kill the cancer these T-cells can also attack normal tissues. But we have worked out the patterns of these toxicities quite well and they’re basically skin, GI tract, liver and the endocrine system. We have developed guidelines for clinicians and they are relatively straightforward in the management, as long as you recognise the pattern and intervene early. So it’s not rocket science and medical oncologists around the country will easily pick this up because they will want to be part of the good outcomes.

And a brief take home message for checkpoint inhibition for doctors coming from this meeting at ASCO?

It’s a brave new world of oncology and watch out solid tumours, here come the checkpoint inhibitors.