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Background Chemotherapy-induced neutropenia (CIN) has been demonstrated to be a prognostic factor in several cancer conditions. We previously found a significant prognostic value of CIN on overall survival (OS), in a pooled dataset of patients with advanced non-small-cell lung cancer (NSCLC) receiving first line chemotherapy from 1996 to 2001. However, the prognostic role of CIN in NSCLC is still debated. Methods We performed a post hoc analysis pooling data prospectively collected in six randomized phase 3 trials in NSCLC conducted from 2002 to 2016. Patients who never started chemotherapy and those for whom toxicity data were missing were excluded. Neutropenia was categorized on the basis of worst grade during chemotherapy: absent (grade 0), mild (grade 1–2), or severe (grade 3–4). The primary endpoint was OS. Multivariable Cox model was applied for statistical analyses. In the primary analysis, a minimum time (landmark) at 180 days from randomization was applied in order to minimize the time-dependent bias. Results Overall, 1529 patients, who received chemotherapy, were eligible; 572 of them (who received 6 cycles of treatment) represented the landmark population. Severe CIN was reported in 143 (25.0%) patients and mild CIN in 135 (23.6%). At multivariable OS analysis, CIN was significantly predictive of prognosis although its prognostic value was entirely driven by severe CIN (hazard ratio [HR] of death 0.71; 95%CI: 0.53–0.95) while it was not evident with mild CIN (HR 1.21; 95%CI: 0.92–1.58). Consistent results were observed in the out-of-landmark group (including 957 patients), where both severe and mild CIN were significantly associated with a reduced risk of death. Conclusion The pooled analysis of six large trials of NSCLC treatment shows that CIN occurrence is significantly associated with a longer overall survival, particularly in patients developing severe CIN, confirming our previous findings.

Lung cancer is predominantly a disease of the elderly with about 50% of diagnoses in patients aged ≥70 years and about 14% in those older than 80. Medical and physiological characteristics of elderly cancer patients make the choice of their better treatment more challenging. Furthermore, aging is accompanied by the so called "immunosenescence" phenomenon, the age-related decline in the immune system that is one of the potential reasons of increase of the incidence and prevalence of most cancers. There is a growing interest in understanding of immunosenescence and how it may correlate with the use of immune checkpoint inhibitors in elderly non-small cell lung cancer (NSCLC) patients. The survival benefit achieved by immunotherapy in all histologies and therapy line settings, added to its manageable toxicity profile, has dramatically changed the scenario of advanced NSCLC treatment. At subgroup analyses of randomized clinical trials, elderly NSCLC population seems to benefit from anti-programmed death-1 (anti-PD-1)/anti-programmed death ligand-1 (anti-PD-L1) agents' treatment. These efficacy data were also confirmed by studies in real-life setting. The key-points of aging and immunosenescence are described, focusing on the role of immune checkpoint inhibitors in elderly NSCLC population.

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