BACKGROUND: Immune checkpoint inhibitors (ICIs) are currently included in the standard of care of the first-line treatment of advanced/metastatic non-small cell lung cancer (NSCLC). However, a relevant group of clinically unfit patients, including poor Performance Status, Elderly, and those with relevant comorbidities, are not represented in most pivotal clinical trials. METHODS: An expert panel meeting commentary was virtually held to point out the key issues in treating such 'invisible' patients and to review the available evidence. RESULTS: Overall, clinically unfit patients represent up to 50% of patients with diagnosis of advanced/metastatic NSCLC. Few dedicated studies with immunotherapy were conducted in this population. Among them, the IPSOS trial finally answers the issue of first line immunotherapy in platinum-unfit patients with advanced NSCLC, demonstrating atezolizumab improved OS and good tolerability compared to monochemotherapy. CONCLUSIONS: Atezolizumab monotherapy can be considered a valid first-line treatment in patients with advanced NSCLC who are unfit to receive platinum-based chemotherapy, including elderly, those with poor PS and/or comorbidities.