Since 2014 more than twenty or thirty new drugs are coming on the market every year, which is unbelievable for what we were accustomed to. When I started work we were dealing with five or ten drugs, and now we have hundreds of drugs. Essentially, the new ones are mainly biological. In this moment what is dealing the research and also the care is immunotherapy, the new immuno-agents, but nevertheless there is still a lot of space for the targeted agent. The difference is that the targeted agents are drugs that are very specific for some kinds of molecular abnormalities in the tumour and usually they are very active. Unfortunately, until this moment they are not curing definitely any patients besides a few cases, but we are able with the research to develop always new drugs against the different pathways of resistance to such targets. This is very interesting because this is prolonging the life and improving the quality of life of our patients, even with metastatic disease, for years. As a matter of fact we multiply by a factor of three or four the overall survival for cancer like colorectal or lung and melanoma, and now we are starting with the gastric and so on, which is very good.
The other group of biologicals are the immuno-agents, these new immuno-agents are drugs that are dealing with our capability to renew tumour cells with our immune system that is somehow inhibited by the cells themselves in a physiological way. This is the way that we have to defend from autoimmunity. Once we discovered this, we were able to create a monoclonal antibody with the capability to reactivate the T-cell activity. The T-cells are those cells that are active after there has been an immunoreaction against something from our body. In this way we are obtaining extraordinary results in at least the majority of cancer we’re treating – not in the majority of patients, but in the majority of cancer. The best results that have been obtained up to now are in melanoma, those tumours that have microsatellite instability – head and neck cancer, lung cancer, especially squamous, and renal – there are already commercially available drugs for this disease everywhere in the world, anal, and so on, so many, many.
What is the difference? It is that activating immunity, we hope that we are going to cure patients definitely. This is the only way, in my point of view, to improve what we call the economic toxicity of this new agent. Because, as everyone is aware, that these new drugs are very expensive and particularly one of the major problems is the sustainability for the social security system like in Italy, where everything is covered by social security, but of course prolonging the treatment for years at costs that are ten or twenty times higher than what we are accustomed to pay for treatment, is going to be a really great problem.
The solution is to cure more people. What we are doing now is trying to understand better since the beginning, how are the characteristics of the tumour? So we are trying to get as much information as we can from the biology of the tumour since the beginning to understand it we can improve the cure rate instead of the care rate. So transformative activity and prolongation of survival in cure. This is going to be the goal of the next few years. The second goal is going to be to understand if we have to prolong treatment, like we’re doing now, or if it’s enough to perform a boost of treatment at the beginning so that we obtain a response, maybe to maintain the results with some time of recall done once in a while instead of every month or every three months, like we’re doing now.
Do you think targeted agents will be used in combination with chemotherapy in the future?
Some of them must be used in combination with standard chemotherapy. I still strongly believe that chemotherapy is not going to die, because, as I told you before, all these new agents are curing a percentage of patients. Unfortunately, targeted agents are very effective on those tumours that have the target, and targets are in 3%, 5%, 10%, when we are lucky 15% of a kind of tumour. That means that the majority of patients usually may have a tumour without the target, or if we put all the targets together, at least half the patients, from half to 75% of patients, have no biological cure with a targeted agent.
Immunity seems to be more active and widespread, but even with immunity we have a very different result in different patient populations. Even there we should consider that we should select those patients that have a higher benefit and understand why it is not working. As a matter of fact, we are developing, as I told you before, my major effort is in phase I, so in new drug development. What we are developing now in many studies is the combination of the new immunological agents – combination between immunological agents, combination between agents and chemotherapy, agents and targeted therapy, and so on.
What is clear up to now is if there is a target driving the tumour growth immunotherapy doesn’t work very much. So for those patients with lung cancer, if they have a mutation of EGFR or rearrangement of ALK or ROS1 or something like that, the results are really disappointing. So for those patients, chemotherapy is better after the targeted therapy has failed, or we are dealing with new targeted agents that are bypassing resistance. In all the other patients immunotherapy can work, especially if there is a high number of mutations inside the tumour it seems to be more immunogenic.
