Yesterday I presented a study about the potential role of liquid biopsy in non-oncogene addicted non-small cell lung cancer. Liquid biopsy is one of the new frontiers in translational oncology but in the field of lung cancer the main applications now are in EGFR mutated disease. What we wish to do is to understand if there is also an application for non-oncogene addicted non-small cell lung cancer and we studied the potential role of dynamic monitoring of liquid biopsy during treatment. So what we saw is that it is possible to predict the benefit from systemic treatment by analysing liquid biopsy at early time points, so at baseline and then after some weeks from the start of systemic treatment. In this way we potentially have the possibility to predict long-term clinical benefit and also, hopefully, to understand which are the patients that should change treatment early. For example, we had one case of hyperprogression in lung cancer in a patient treated with immunotherapy and we had an exceptional increase in the level of a mutation in the blood. So we had a completely different behaviour with respect to the other population of patients. So maybe in the future if we can confirm this data we can use liquid biopsy assessed maybe some weeks after the beginning of the treatment to predict the risk of hyperprogression even. So this will be very relevant.

Just to check, how many samples were you working with in this study?

We have prospectively enrolled until now all the patients receiving systemic treatment, so either chemotherapy or immunotherapy. At the moment of the data analysis we had collected 162 cases and samples and we had analysed tissue from 87 samples. We have detected tumour associated genetic alterations and the data I have presented were about the subgroup of patients that carried the KRAS mutations. So we had analysed patients who were KRAS positive in tissue until now. We had 44 cases of KRAS mutated patients and we analysed them in plasma during treatment. So now we are also analysing the other patients by using NGS in plasma, so by analysing the other sentinel mutations, and we are going on enrolling other patients. So we are planning to have a higher number of patients maybe at least 100 patients treated only with immunotherapy to be analysed maybe by the beginning of next year to confirm the results.

The patients that have been analysed so far, any unexpected markers coming up alongside the KRAS-3 alterations?

We have analysed KRAS mutated patients in plasma by using Droplet Digital PCR. So in this analysis, the first preliminary analysis, we had only the possibility to understand how the level of mutation changes during treatment. So we analysed only KRAS mutation. In the other patients which we are analysing by NGS we can also explore these secondary points if there is a change, for example among KRAS mutated patients it could happen that patients’ KRAS mutations drop and, for example, p53 rises. So this may have a strong significance from the biological point of view but we are analysing this data in the next month probably.

And if anyone wanted to get involved and help with patient recruitment for an expansion, is that ongoing and where can they be in contact?

Yes, until now it is a mono-institutional study so we are going on enrolling patients treated with immunotherapy but we are open-minded and we hope to increase the number of patients. I think it will be feasible because now we are using tissue and plasma by using Streck tubes so we can process them within two or three days. So there is also the time for sending samples, yes, it is possible.

Well done, we look forward to hearing more from more data as it becomes available maybe this time next year.

In which sense do you mean?

I’m saying we look forward to hearing more from the study maybe at ESMO 2019 with more data, more patients.

Yes, hopefully.

That covers my notes and questions, is there anything else that you would like to add, any further detail?

I think that the main point is that liquid biopsy may be used to monitor tumour burden and to help in understanding the response to treatment. Also the most important application is if we have the possibility to customise treatment in the field of immunotherapy, so to understand if there are patients that don’t need more intensified treatment, for example combination treatment, because we know that they are a good prognostic group and other patients that, on the contrary, need to change treatment or to add chemotherapy and so on. So this is the most important application so we are happy to expand our data and to add information by using NGS because we can understand if there is a role for co-mutations and changing the genotyping during treatment and so on