ELCC 2021 | Management of patients with PDL1-high advanced NSCLC

This is a very important session during the European Lung Cancer Conference because we will discuss about management of patients with non-small cell lung cancer with high levels of PD-L1 expression. Because for these patients, we have a lot of potential questions, and, mainly, of course, the most important point is, what is the best therapy we need to deliver to these patients?

So in this symposium, we, this is a symposium I will chair together with Dr Landi and she will present the beginning of the symposium, a case, a clinical case. She will simulate some questions around the options that we have for a patient with the characteristic that she will present.

And we have different conditions, of course. The main point is, for example, what is the role of the presence of brain metastasis, and so what should we do in the presence of brain metastasis? And of course, also other options, including single-agent immunotherapy, that is one of the potentialities that we have, or combinations without chemotherapy. Or combinations including a small, a limited number of cycles of chemotherapy, or the combination, the classical combination of chemotherapy and immunotherapy.

So other colleagues will present the data on the other options. And my focus will be specifically on the combination of immunotherapy and chemotherapy, and I will start saying that, unfortunately, in patients with high levels of PD-L1 expression, we still have a consistent proportion of them, approximately 30%, of these patients are not benefiting at all from immunotherapy. This is what clearly emerges when we look at the curves of the clinical trials, because at the beginning we have an overlap of the curves. And probably patients receiving mono-immunotherapy could do survival less than patients treated with chemotherapy.

So we cannot exclude at the beginning that meaning in some patients, 30% of them, even a detrimental effect of immunotherapy, even if the patient presents high levels of PD-L1 expression. This is the most important point, explaining why many investigators prefer using combinations, and why several studies are focusing on the combination of immunotherapy with something else, chemotherapy, or even other immunotherapeutic agents, in order to improve the results, particularly in this group of patients.

So, in my presentation, I will analyze all the data we have today, and I’m personally convinced that based on the options that we have available at the present time, that chemo-immunotherapy is probably the best option we can offer to these patients, even if they display high levels of PD-L1, even if we know that we increase toxicity.

And one important point that we need to consider is particularly the risk of adverse events. Because of the toxicity, clearly chemo-immunotherapy is not the option that we can use in all patients with non-small cell lung cancer. But, of course, we need to consider these options, particularly for those individuals with a good performance status, and particularly for individuals in which there is a consistent risk of rapid progression of the disease.

So, these are probably the two groups of patients in which this option clearly is better than single-agent immunotherapy. Even if we don’t have formally any clinical trial comparing single agent versus the combination in patients with high levels of PD-L1 expression.