Could you tell me, you’re looking here at immunotherapy for lung cancer, you’re looking at early stage, fairly early stage, curable lung cancer, cancer cured by resection, what were you trying to do here?

For these patients after lung cancer surgery the cure rate is about 40% and ten years ago we learned with adjuvant chemotherapy it could be 45%. So our current treatment is surgery, often with chemotherapy. Since ten years ago nothing happened for these patients so MAGE-A3 cancer immunotherapy is a kind of vaccination against a protein on lung cancer cells, the lung cancer cells that are responsible for the relapse of the patients after surgery. So with this therapy we wanted to test if we can improve cure rates in these patients.

And there was a good rational basis for believing it could?

Yes, because on the one hand patients after lung cancer surgery are often weakened so a mild, gentle therapy, as cancer vaccination, would be very welcome to them. On the other hand, we knew from previous data in melanoma that this type of strategy, MAGE-A3 cancer immunotherapy, could induce responses in a difficult to treat disease as metastatic melanoma and we had signals in early non-small cell lung cancer resected that it improved, in a small phase II study with about 200 patients, a randomised study, that it improved cure rates in lung cancer.

Now you’ve been using MAGE-A3 in a phase III study, thousands of patients. Can you tell me what was the protocol, what did you do?

In that setting to validate the hypothesis in a solid way you need a large number of patients and you need a very well designed strong study, that is what we tried to do. Because the MAGE-A3 protein is present in about one third of lung cancer patients we had to screen, at the end of the day, about 14,000 patients after lung cancer surgery. So we looked for the expression of the target, the MAGE-A3, first and in these patients expressing the target we then looked for eligibility and then they were randomly assigned, 2:1 randomly assigned. Two had MAGE-A3 vaccination and one had exactly the same schedule of placebo vaccination. We randomised a total of 2,300 patients so by that it’s the largest therapeutic study ever done in lung cancer.

Impressive indeed and this is against a backdrop of a cure rate which had risen to 45% with adjuvant chemotherapy. What did you find?

Unfortunately for investigators and patients we did not find that the MAGE-A3 cancer immunotherapy improved the outcome results. What did we find? It was a global trial and in communication with all the disciplines around the globe, surgeons, oncologists, we found that with modern approaches of surgery and adjuvant chemotherapy, so with our standards, that in this very large group of patients globally the outcome was about 50%. So we made some progress, not by this treatment but overall we set a new benchmark. But unfortunately the MAGE-A3 cancer immunotherapy did not meet its endpoint.

So it appears to have no significant signal here. What can we learn about this, because the use of immunotherapy is attractive, isn’t it?

Yes. What we learn is that there are two types of immunotherapy. There are the antigen specific strategies which are cancer vaccinations in the true sense and there are the immunomodulation strategies with checkpoint inhibitors which are very much in our focus nowadays. What we learned here is that we tested the strategy of vaccination in probably the appropriate patient group, those with minimal residual disease after surgery, in a very large, methodologically sound trial. What I learned from this is that our current technologies of lung cancer vaccination are not the way forward. We need to be more inventive; we need to find other solutions because this trial is really a landmark trial, I think, and it gives an answer that our current vaccination strategies in lung cancer do not work.

What is the brief summary message that you would leave cancer clinicians with?

We should not leave the field of immunotherapy. Certainly with checkpoint inhibitors there may be a future for the combination of vaccination and checkpoint inhibitors so there’s a lot on-going in immunotherapy but the vaccination strategies as we have them, anno 2014, are not the ones that will help us forward.