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Efficacy of PD-1 & PD-L1 inhibitors in older adults: a meta-analysis.

Efficacy of PD-1 & PD-L1 inhibitors in older adults: a meta-analysis.
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Elias R, Giobbie-Hurder A, McCleary NJ, Ott P, Hodi FS, Rahma O,


Elias R, Giobbie-Hurder A, McCleary NJ, Ott P, Hodi FS, Rahma O, (click to view)

Elias R, Giobbie-Hurder A, McCleary NJ, Ott P, Hodi FS, Rahma O,

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Journal for immunotherapy of cancer 2018 04 046(1) 26 doi 10.1186/s40425-018-0336-8

Abstract
BACKGROUND
Immune checkpoint inhibitors targeting PD-1/PD-L1 pathway demonstrated promising activities in variety of malignancies, however little is known regarding their efficacy in adults aged ≥65 years.

METHODS
We conducted a systematic review and a study-level meta-analysis to explore efficacy of ICIs based on age, younger vs older than 65 years. We included in this analysis randomized controlled phase II or III studies in patients with metastatic solid tumors that compared efficacy of PD-1 or PD-L1 inhibitors to a non-PD-1/PD-L1 inhibitor. Aggregated estimates of overall survival (OS) and progression-free survival (PFS) are based on random/mixed effects (RE) models to allow for heterogeneity between the studies.

RESULTS
Initial search identified 53 articles, 17 were randomized controlled trials that compared nivolumab, pembrolizumab or atezolizumab to chemotherapy or targeted therapy. Only 9 trials reported hazard ratiios (HR) for OS based on age and were included in this meta-analysis. Out of those studies seven reported HR for PFS but only 4 studies included subgroup-analysis based on age for PFS. The overall estimated random-effects HR for death was 0.64 with 95% CI of 0.54-0.76 in patients ≥65 years vs. 0.68 with 95% CI of 0.61-0.75 in patients < 65 years. The overall estimated random-effects for HR for progression was 0.74 with 95% CI of 0.60-0.92 in patients ≥65 years vs. 0.73 with 95% CI of 0.61-0.88 in patients < 65 years. CONCLUSIONS
PD-1 (nivolumab and pembrolizumab) and PD-L1 (atezolizumab) inhibitors had comparable efficacy in adults younger vs ≥ 65 years.

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