The Role of Immunotherapy in the First-Line Treatment of Elderly Advanced Non-Small Cell Lung Cancer

SIMPLE SUMMARY: The treatment of advanced non-small cell lung cancer (NSCLC) after the age of 65 raises age-related problems as the elderly are often affected by other diseases, not infrequently chronic, take drugs that may interfere with anti-cancer treatment and are sometimes unable to fully understand relevant information. Moreover, they do not represent the ideal patient for enrolment in clinical trials, even with immunotherapy, which is now the choice therapy for the first-line treatment of NSCLC. With a view to offering more time to patients with metastatic NSCLC, the issues of quality of life and appropriateness of oncological care in the elderly are of primary importance. This review stresses the need to find a common approach to lung cancer management in a steadily aging society and describes the main currently available data on the use of immune checkpoint inhibitors in older patients with advanced NSCLC, confirming the necessity for reliable biomarkers that predict immune response to assess which patients benefit from which type of immunotherapy. ABSTRACT: Immune checkpoint inhibitors have changed the history of NSCLC treatment by becoming, alone or in combination with platinum-based chemotherapy, a mainstay of first-line therapy for advanced NSCLC. This increasingly dictates the identification of predictive biomarkers of response that can guide patient selection, in order to rationalize and personalize therapies, particularly in elderly patients. Immunotherapy in these patients raises questions of efficacy and tolerability related to aging, which is accompanied by a progressive decline in various body functions. Physical, biological and psychological changes contribute to individual validity status and, preferably, ‘fit’ patients are generally enrolled in clinical trials. In elderly patients, especially frail and complex patients with more than one chronic disease, data are poor and specific prospective studies are needed. This review reports the main available results on the use of immune checkpoint inhibitors in older patients with advanced NSCLC, in terms of efficacy and toxicity, and aims to highlight the need to better predict which patients might benefit from immunotherapy agents by probing knowledge and integrating information on immune system changes and age-related physiopathological modifications.