Abstract 1089P
Background
Immune checkpoint inhibitors (ICIs) have had major roles in therapy of advanced non-small cell lung cancer (aNSCLC). A study has shown that T cell-promoted tumor ferroptosis, a form of iron-induced cell death, is involved in the anti-tumor activities of ICIs. While malignant cells often require high amounts of iron for proliferation, iron also facilitates the production of oxygen radicals, which may result in ferroptosis. Little is known about efficacy of ICIs on aNSCLC with iron metabolism disorders. Our aim was to examine outcomes for patients prescribed anti-PD1/PDL1 antibody monotherapy for aNSCLC and tumor proportion score (TPS) of hepcidin, a key regulator of iron metabolism.
Methods
This retrospective observational study was conducted using data of histologically confirmed aNSCLC patients with samples for hepcidin immunohistochemical staining. Eligible patients initiated nivolumab, pembrolizumab or atezolizumab monotherapy as any line of treatment from January 1, 2016, to August 24, 2018; data cutoff was March 31, 2021. The Kaplan-Meier method was used to estimate time to progression (TTP). Statistical analysis was conducted using GraphPad Prism 9.
Results
The 45 eligible patients included 39 (86.7%) men; the median age was 72 years (range, 36-83 years); 3 (6.7%) of 45 patients with driver gene mutations. The median patient follow-up was 4.0 months (range, 18 days to 61.0 months). The median TTP was not reached (95% CI, 25.1-45.5 months) and 4.2 months (95% CI, 11.9-18.6 months) for hepcidin High (TPS ≥ 50%) and Low and None (TPS < 50 %), respectively. The hazard ratio (HR) and p value for TTP with hepcidin High versus Low and None were 0.31 (95% CI, 0.13 to 0.78) and p = 0.087.
Conclusions
aNSCLC patients with hepcidin TPS high may highly benefit from anti-PD1/PDL1 antibody monotherapy. Further evaluation with large numbers of cases is needed to explore the role of hepcidin as a predictive biomarker for anti-PD1/PDL1 antibody treatment.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
JSPS KAKENHI Grant Number 20K08571.
Disclosure
All authors have declared no conflicts of interest.