Hôpital Rene Muret, HUPSSD, UCOG 93 (APHP), Sevran, France
Thierry Landre , Cherifa Taleb , Patrick Nicolas , Gaetan Des Guetz
Background: The immune system undergoes profound transformations with age, and response patterns to immune challenges are therefore highly age dependent. Nivolumab, an anti-PD-1 immune checkpoint inhibitor, showed promising activity and tolerability in several solid tumours. However, in our knowledge, few data are available in patients older than 75 years. Methods: We performed an age subgroup analysis of published randomized control trials concerning nivolumab versus standard therapy in previously treated patients with advanced solid tumours. Overall Survival (OS) among the elderly ( ≥ 75 years) was compared with that of younger patients ( ≥ 65 to < 75 years). Hazard ratios (HRs) with their 95 % confidence interval (CI) were collected from the studies and pooled. A fixed-effect model was used. Results: Few studies have been published corresponding to our inclusion criteria. Two studies (CheckMate 017 for Squamous and CheckMate 057 for Non-Squamous) assessed nivolumab versus docetaxel in Non-Small Cell Lung Cancer (NSCLC) and one study (CheckMate 025) assessed nivolumab versus everolimus in Renal-Cell Carcinoma (RCC). Our pooled-analysis included 146 patients older than 75 years (72 NSCLC, 74 RCC) and 541 patients between 65 and 75 years (291 NSCLC and 250 RCC). All patients were mostly men (68%), with good Performance Status (0 or 1). For patients ≥75 years, OS of the nivolumab arm was inferior to that of the control arm (HR = 1.22; 95% CI 0.80-1.85; p = 0.36). Conversely, among younger patients (≥65 to < 75 years), a statistically significant OS benefit was seen with nivolumab (HR = 0.62; 95 % CI 0.50-0.77; p < 0.0001). Similar trends were observed for PFS in patients with NSCLC (HR = 1.24; 95 % CI 0.73-2.09; p = 0.43 for patients ≥75 years and HR = 0.78; 95 % CI 0.60-1.01; p = 0.06 for patients ≥65 to < 75 years). Conclusions: Nivolumab survival benefit in patients older than 75 years appears uncertain. Several significant changes in the elderly individuals in regulatory elements of CD4+ and CD8+ T cells could explain the lack of effectiveness of nivolumab.These results should be interpreted with caution due to the small number of patients. Further studies are warranted to evaluate anti-PD-1 efficacy in elderly.
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