Personalised treatment of non-small-cell lung cancer patients — review of current evidence

Abstract

The increasing number of scientific reports on the new-generation tyrosine kinase inhibitors and immunological checkpoint inhibitors in the management of patients with non-small-cell lung cancer (NSCLC) results in the necessity of frequent guidelines updating and constant preparing of treatment algorithms by scientific societies. This is accompanied by the continuous search for molecular predictive factors that could allow more personalised treatment and increased therapeutic benefits achieved by patients. Based on current recommendations, patients with mutated EGFR or rearranged ALK genes in advanced NSCLC should begin their treatment with tyrosine kinase inhibitors. The use of these agents within first- and second-line treatment may produce significant improvement of prognosis in selected patients. The improvement of survival may be achieved in patients with central nervous system metastases, who have poor prognosis. The role of immunotherapy increases as well, but negative results of some trials (e.g. MYSTIC or CheckMate 026) indicate difficulties in precise defining of groups of patients with the highest chances of benefit from immunotherapy. In view of the results from some trials (e.g. CheckMate 017, KEYNOTE 021, or PACIFIC), PD-L1 expression is not an optimal biomarker for immunotherapy. Initial results of some studies and retrospective analyses suggest the predictive value of other genetic or molecular abnormalities (e.g. high mutation load in tumour genome, microsatellite instability, or repair mechanism abnormalities). Precise definition of new biomarkers and ensuring the availability of genetic testing appears to be mandatory before widespread use of immunotherapy in clinical practice. Recently published positive results of studies testing new targeted agents, which have high value predictive factors, will probably influence the updates of scientific societies’ guidelines and management algorithms. The aim of this review was to assess possibilities of personalised treatment in patients with advanced NSCLC with the use of new generation tyrosine kinase inhibitors and immune checkpoint inhibitors, in view of new scientific reports.