WCCS 2016

VISMO trial to treat basal cell carcinoma

Prof Axel Hauschild - University of Kiel, Kiel, Germany

At this conference I was talking about various clinical trials. On the one hand is the clinical trials on the so-called targeted therapies, so the MEK and BRAF inhibition, and the latest results, it was an update, on these clinical trials, namely dabrafenib and trametinib, and on the other hand vemurafenib and cobimetinib. Also I’m talking about divisions on targeted therapies, how they will be used in the future. On the other hand, it’s immunotherapy which is an attractive topic at this conference and it’s the PD1 antibodies which are making the difference nowadays in combinational treatment of nivolumab and ipilimumab, namely which is becoming standard of care if overall survival data are available but they are not available at the moment. So this conference will not contribute to the knowledge of the overall survival of the combo.

So VISMO is approved since 2012 in Europe and it’s a drug which is making a difference. The only active systemic treatment for advanced basal cell carcinomas, locally advanced as well as metastatic basal cell carcinomas. It presented already response rates of almost 60%, the response duration was, in an update, around 2.5 years and there are roughly 30% of patients who have a complete response. Therefore it’s a discussion if this is standard of care for these rare subtypes of basal cell carcinomas.

Could you tell us more about your current studies?

There are various BRIM studies so one is BRIM3 and in two months from now we will learn more about the four year survival of BRIM3. It was a trial which was bringing vemurafenib to the market so it was a comparison of vemurafenib and DTIC, so conventional chemotherapy, and we have presented a pooled analysis of various BRIM studies here. We conducted a pooled analysis of predictive factors for response and for long-term survival of either BRIM3, which is vemurafenib compared to DTIC, BRIM7 which is cobimetinib and vemurafenib, and coBRIM which was a clinical trial bringing the combination to the market. This was comparing cobimetinib/vemurafenib to vemurafenib alone. So it was setting a new standard of care and the new standard of care is a combination of BRAF and MEK inhibition. This study showed that there is very good long-term survival, particularly in those patients who have low LDH levels when we initiate the treatment. So the simple blood marker of LDH is making a difference in the prognosis of the patient but also it’s a predictive factor for response. The patients have better responses and long-term survival once they have low LDH.

Could you tell us about the checkpoint and KEYNOTE trial?

The checkpoint, it’s called CheckMate trial, and KEYNOTE, it’s more or less a clinical trial on the PD-1 antibodies. We have no new data here but two months ago at the ASCO meeting in Chicago there were releases of long-term survival and there is surprisingly long survival after four years. We have data already for nivolumab after five years in the range of 32-33% of patients surviving five years which is an outstandingly good result. Don’t forget six years ago we had a long term survival of five years in 5% of the patients so we have an enormous increase in overall long-term survival and this is something really making a difference. So the PD-1 antibodies are making a difference but, as I pointed out, PD-1 plus ipilimumab could make another difference but there is no long-term survival data available. We need to wait for overall survival.

Who pays for all of this?

That’s a very good question and there was a presentation at ASCO in the Health and Economy session. I can tell you in Germany we have a very good situation – once a drug is approved on the European level it’s immediately paid by the health insurance companies for everyone. So it’s very fortunate. Then within the next twelve months the companies need to demonstrate the superiority of the new drug compared to the old standard of care. Once they demonstrate a high difference, big difference, the magnitude of benefit is exciting, they get a good price; if it is less good they receive a lower price. That is a very fortunate situation but the dilemma in Europe is in very many countries the drugs are approved but they cannot be used, they are simply not paid. It’s a long time in other countries before the drug is paid, if it is paid at all, and then we have countries, particularly in Eastern Europe, where none of the new agents is available, they are approved but nobody can afford it because the patients need to pay it out of the pocket. This is a dilemma and here was a presentation, and at ESMO in six weeks from now is another presentation, of our organisation who is running this congress, the EADO, and this is a study conducted by Lydia Sekulovic from Belgrade. She pointed out that 5,000 patients in Europe with metastatic melanoma are not receiving the new agents because they cannot pay for it. I think this is a dilemma and we need to work on it.