Lung Immunotherapy in the Elderly with NSCLC – the Who, the What, and the When

Lung cancer remains the deadliest solid tumour, and incidence trends are still on the rise despite aggressive anti-smoking policies. Non-small-cell lung cancer (NSCLC) is diagnosed in approximately 85% of all new lung cancer patients, of which over 50% are elderly. Checkpoint inhibitors (ICIs) are a new class of anti-cancer drugs that have revolutionized NSCLC treatment and numerous large phase III trials have confirmed their efficacy and safety. Despite no longer being explicitly excluded from clinical studies, elderly patients are still vastly under-represented in almost all of these trials, often due to issues of comorbidities or poor performance status. The aim of this chapter is to review available evidence from elderly subgroups analyzed in clinical trials, phase II elderly-focused trials, and real-world data in order to underline the safety and efficacy of checkpoint inhibitors in aged individuals. The first part focuses on identifying which of the elderly can benefit from immunotherapy, with reference to chronological age, performance status, comorbidities, concurrent medication, geriatric assessments, PD-L1 values, and immunosenescent phenotypes. The second part of the chapter focuses on data from different ICI-based treatment regimens used as single-drug therapy, chemo-immunotherapy, or combined immunotherapy with the goal of underlining which drugs have the most benefit in elderly patients. The third part of the chapter discusses the optimal timing of ICI treatment in relation to radiation therapy and prior chemotherapy exposure, with an additional focus on the importance of the time-of-day delivery of ICI treatment.