EADO Congress 2015

How should we handle talimogene laherparepvec (T-VEC)?

Prof Axel Hauschild - University of Kiel, Kiel, Germany

We have some news here from Marseilles at the meeting, it’s a hot topic that in fact a couple of compounds have been approved. First of all T-VEC, tell me about T-VEC, that’s hot off the press, isn’t it? What’s the significance of T-VEC being approved by the FDA?

Yes, it’s a viral based vaccine, T-VEC which can be used intralesionally for patients. It’s stimulating GM-CSF which is an immunomodulatory cytokine. It’s leading to a regression of the injected lesions but also non-injected lesions. The FDA very recently approved T-VEC as an agent for non-resectable stage 3 disease and stage 4 disease. In Europe this week the CHMP committee of the EMA was releasing a press note which is saying that it’s a positive opinion for T-VEC in Europe as well but this will be restricted to patients with just stage 3 disease which is unresectable and stage 4 so-called M1a category. So they don’t want to see patients with lung, liver, bone and brain mets, it’s the patients with limited disease to soft tissue.

Now this is early therapy, isn’t it?

It is very early therapy so it will be approved for first line treatment. This is what the data are saying and I think it is good news because we have another player on the market and another effective agent on the market.

How do you see it being added to the other therapies, the targeted therapies and the immune therapies?

I don’t think that it’s so much competition because T-VEC is more or less filling a gap. So it’s a gap of the lesions from stage 3 disease which is unresectable and M1a. So if you have huge tumour volumes, you have ten lung mets plus liver mets and the patients are carrying a BRAF mutation it’s a good candidate for BRAF and MEK inhibition or for PD1 antibody. So this was never in the past a good candidate for a T-VEC injection. And you need to have injectable sites which means injectable metastases in the skin or in the lymph nodes. So you need to have some prerequisites which are excluding some patients from the use.

So which patients will you be using it for?

I would use it for non-resectable soft tissue metastases. If these patients have otherwise no organ infiltration, which means stage b and c of the M1 category.

Now we’re also seeing a licence for adjuvant ipilimumab. That’s quite different from the way it has been used so far, or licensed so far. What do you reckon about that?

That was a bit of a surprise for me. I don’t know if the FDA who approved the agent today have seen data which I have not seen. So the latest data I have seen is the 10% difference in disease free survival of high dose ipilimumab compared to observation alone which means placebo infusions. Ipilimumab was given in a dose of 10mg/kg and the approved regimen is 3mg/kg so it’s more than tripling the dose plus it’s not given for just four cycles in a three month period, it’s given for three years now. So it’s a much higher dose given for a much longer time, or a significantly longer time, and there is some toxicity. So the outweigh of, let’s say, effect in terms of clinical benefits and the toxicity is somewhat critical.

And will you be using it in that role?

I will not immediately use it, even if it is approved in Europe because I believe it’s toxic and also we need to discuss for this agent the price because ipilimumab is not a cheap treatment and we are giving it for just four cycles. If we need to give it for a total of three years I would love to see differences which are larger than 10% in disease free survival; I would love to see overall survival differences and, in addition, we need to have a good management of the toxicity.