Background: In the recent years, immunotherapeutics and specifically immunecheckpoints
inhibitors have marked a significant shift in the diagnostic and therapeutic algorithm of
Non-Small Cell Lung Cancer (NSCLC), allowing us to use immunotherapeutics alone or combined
with chemotherapy for a great subset of patients. However, new interesting approaches are being
presently investigated, markedly immunotherapy combinations, that is, the use of two or more immunotherapeutics
Methods: In particular, the combination of anti-PD-1 nivolumab and anti-CTLA-4 ipilimumab has
already provided groundbreaking positive results in the advanced NSCLC and other combinations
are currently under investigation.
Results: Therefore, this paper aims to provide a comprehensive state-of-the-art review about immunotherapy
combination, along with suggestions about future directions. A comprehensive literature
search was carried out to identify eligible studies from MEDLINE/PubMed and ClinicalTrials.gov.
Conclusion: Nivolumab plus ipilimumab represent the most promising immunotherapy combination
for the treatment of advanced NSCLC patients; safety, tolerability and efficacy of new immunotherapeutics
(in monotherapy and in immunotherapy combinations) must be further assessed in