Abstract 23P
Background
Immune checkpoint inhibitors have significantly improved survival in advanced-stage non-small cell lung cancer, but the majority of patients do not obtain (long-term) benefits. Pembrolizumab clearance could serve as a prognostic biomarker for survival and identify non-responders early in treatment as it is a proxy for cancer cachexia. We investigated pembrolizumab clearance as an early prognostic biomarker.
Methods
Pembrolizumab clearance was calculated using non-linear mixed effects modeling. Cut-points of pembrolizumab-clearance were calculated using maximally selected rank statistics. The prognostic value of early pembrolizumab clearance (normalized to a standard lean body weight) for survival was estimated using the precalculated cut-points and a univariate Cox regression analysis. The performance of identifying non-responders and responders (defined as disease control at 8 months) of the identified cut-points was assessed by calculating sensitivity, specificity, true positive value (TPV) and true negative value (TNV).
Results
A total of 303 patients were included for analysis; 65% of these patients experienced disease progression and 60% died. Patients with a weight-normalized pembrolizumab clearance above 0.232 L/day at the first dose were more likely to have progressive disease (HR=1.98, 95% CI [1.21, 3.26], p=0.007) or poor survival (HR=2.04, 95% CI [1.16, 3.59], p=0.014). A diminished decrease in clearance (
Conclusions
These results show that early pembrolizumab clearance is a highly sensitive prognostic biomarker to identify treatment responders, and TPV may be improved by combination with other biomarkers.
Clinical trial identification
NCT04909684.
Legal entity responsible for the study
DEDICATION study group.
Funding
Stichting treatmeds.
Disclosure
All authors have declared no conflicts of interest.