The expression of the PD-L1 receptor is the key criterion for qualifying patients for the first-line treatment of advanced non-small cell lung cancer. Prof. dr hab. n. med. Joanna Chorostowska-Wynimko, Secretary General of the European Society of Lung Diseases, Deputy for Research, Director of the Institute of Tuberculosis and Lung Diseases and Head of the Department of Genetics, Clinical Immunology at the Institute of Tuberculosis and Lung Diseases in Warsaw, explains why it is so important when immunotherapy is used.
From 2018, Polish patients have access to immunotherapy in the first line of NSCLC treatment (non-small cell lung cancer). A qualifying factor for this therapy is the expression of the PD-L1 protein. What is PD-L1 expression and why is it so important for immunotherapy? Should every patient in Poland diagnosed with NSCLC undergo a diagnostic examination in this direction?
Prof. dr hab. n. med. Joanna Chorostowska-Wynimko: Each of the innovative, personalized therapies used in modern oncology is characterized by the use of biomarkers that allow to precisely identify a group of patients in whom the likelihood of responding to a given type of treatment is particularly high. In the case of first-line immunocompetent therapy in patients with non-small cell lung cancer, it is PD-L1 protein expression on neoplastic cells.
It should be remembered that immunotherapy is intended for patients with a generalized form of non-small cell lung cancer and each patient, both with adenocarcinoma and squamous cell carcinoma, should be diagnosed with PD-L1 protein. Unless, in the opinion of the attending physician, there are contraindications that prevent the use of this type of treatment.
Can it be said that the higher the expression of PD-L1, the more effective the treatment? Can PD-L1 expression change over time with disease progression?
Current knowledge indicates that the group of patients in whom we expect a response to immunotherapy are those with the expression of PD-L1 protein on neoplastic cells equal to or higher than 50%. Recent studies show that the higher this percentage, the greater the likelihood that we will respond to the treatment, i.e. the treatment will actually be effective.
Immunotherapy, as the name suggests, is a treatment with a very unique philosophy of action, closely related to the activity of the immune system. We do not act directly on the neoplastic cell – the aim of this therapy is to stimulate the host’s immune system response against neoplastic cells; Our goal is that the patient’s immune system will eliminate or inhibit the development of the neoplasm by itself.
The activity of the immune system is an extremely important element of the defense response to the cancer that develops in the patient’s body. An inherent feature of the immune response is also its variability. This also applies to PD-L1 expression, which can change over time and even within the neoplastic lesion. This variability makes PD-L1 expression unfortunately not an ideal biomarker.
Are there any other biomarkers qualifying the patient for immunotherapy?
As of today, the expression of the PD-L1 protein is the only reliable biomarker that we can use with full responsibility as a tool for qualifying NSCLC patients for immunotherapy treatment. At the same time, the search for other potential indicators that will allow even more effective use of this treatment is ongoing.
A biomarker with high hopes, although its diagnostic value has not yet been fully confirmed, is the mutational burden. This is a very sophisticated biomarker using
the number of mutations, genetic disorders, present in the cells of the cancer developing in the patient’s body is assessed. The more of them, the more genetically diverse the tumor and the greater the chance that it will trigger a response of the patient’s immune system, and thus the greater the chance that immunocompetent drugs will be effective in the fight against cancer. Of course, as I mentioned, at the moment it is not certain how to determine and interpret the mutational load in order to use this marker with full responsibility for the qualification of patients for treatment.
What about patients with less than 1% PD-L50 expression? Do such patients have access to innovative immunotherapy?
In Poland, these people do not have access to first-line immunotherapy. As I mentioned, the universal, commonly used criterion allowing the initiation of monotherapy with an immunocompetent drug in the first line is the expression of the PD-L1 protein at least equal to 50%. In the world, for patients who do not meet the 50 percent criterion an alternative is available in the form of combining immunotherapy with chemotherapy. We do not have such a possibility in Poland. However, in the second line of treatment, both in Poland and worldwide, we use immunotherapy only on the basis of clinical criteria. In this group of patients, PD-L1 expression is no longer significantly predictive.