Immunotherapy with Pembrolizumab improves treatment of advanced lung cancer

Staining of tumor tissue: detailled genetic and biochemical investigation allows precisely fitted treatment

Patients with advanced non-small-cell lung cancer may reckon with considerable improvements for their therapy. This is the promising result of a clinical study testing the antibody Pembrolizumab. Results of the study have been published recently in  the renowned New England Journal of Medicine by a research team around first author Prof. Dr. Martin Reck (LungenClinic Grosshansdorf, DZL site ARCN).

Immunotherapies with antibodies are currently revolutionizing the treatment of cancer, because they are more targeted and have fewer side effects than standard chemotherapies. Therefore, expectations about the outcome of the phase III study ‘KEYNOTE-024’ were high. As in the study with the antibody Nivolumab (published last year), PD-1 was chosen as target. PD-1 and its receptor PD-L1 enable the tumor to escape from immune surveillance (see article on Nivolumab for further information on the active principle). Both antibodies – Nivolumab and Pembrolizumab, which was used in this study – recognize PD-1 and prevent it from binding to PD-L1. In contrast to the Nivolumab study, only such patients with advanced non-small-cell lung cancer (NSCLC) were treated with Pembrolizumab that displayed high expression of PD-L1 on tumor cells. The results were very promising: In comparison with standard chemotherapy, patients treated with Pembrolizumab achieved longer overall survival, a longer period without progression and fewer severe side effects. Moreover, tumors responded better and longer to immunotherapy than to chemotherapy. Solely side effects concerning the immune system were observed more often.

It is an aim of clinical research to develop therapies that are more precisely fitted to one patient’s cancer. These therapies have the advantage that they often have fewer side effects. Consequentially, patients are phenotyped in a more detailed fashion before treatment starts: Physicians look into genetic status of tumors as well as into the protein expression. Thus, such patients can be identified which exhibit certain mutations – in the EGF receptor, e.g. – and treated with tyrosine kinase inhibitors specific for this receptor. Unfortunately, the numbers of patients with specific mutations are quite low. In contrast, 30% of patients with advanced NSCLC have an elevated PD-L1 expression, implying that improved treatment with Pembrolizumab is possible for this large fraction of patients. “This new option will change diagnosis and therapy of previously untreated patients fundamentally”, says Prof. Dr. Martin Reck (LungenClinic Grosshansdorf). “We have to identify patients with high PD-L1 expression as early as possible, because we have a substantially improved method of treatment in our hands now.” It is expected that Pembrolizumab will be approved by the regulatory authorities in the coming months.  

Further information: Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O’Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR, for the KEYNOTE-024 Investigators (2016) Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med 375: 1823-1833 (ARCN)

External link to the article

Video of an interview with Martin Reck by the German Cancer Society [in German]



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