Abstract 360P
Background
Programmed death-ligand 1 (PD-L1) expression level generally shows a positive relationship between response and survival but it has not proved useful as a predictive marker in second or further lines of therapy for NSCLC. LAG-3 and CD-155 inhibit antitumor immunity by interacting with various receptors and are targets for recently developed anti-LAG-3 and anti-T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) agents. We investigated relationship between the expression levels of LAG-3 and CD-155 with overall survival (OS), progression-free survival (PFS), and overall response rates (ORR).
Methods
78 metastatic NSCLC patients who received nivolumab as second-line treatment after conventional chemotherapy were included. LAG-3 expression levels in tumor-infiltrating lymphocytes (TIL) and stromal lymphocytes (33 patients) and cytoplasmic and membranous CD-155 expression levels in tumor cells (61 patients) were evaluated by immunohistochemistry (IHC), and the relationship of the expressions with OS and PFS have been estimated with Kaplan-Meier method.
Results
Median OS of all patients was 8.7 months (95% CI: 5.1–12.3). We did not find any association between CD-155 and LAG-3 expressions and OS, PFS, and ORR. Median OS was 6.4 months (95% CI: 4.9–7.8) in patients with high CD-155 expression, and it was 11.3 months (95% CI: 6.9–15.8) in the low group (p=0,53). Positive LAG-3 expression in TIL was associated with a median OS of 6.8 months (95% CI: 5.1–8.6) while median OS was 6.9 months (95% CI: 2.3–11.5) in the negative group (p=0.8). Multivariate analyses identified poorer ECOG performance score, squamous histology, anemia, hypoalbuminemia, high pan-immune-inflammation value, and radiotherapy to the lung before nivolumab treatment as unfavorable independent risk factors for OS.
Conclusions
Our study could not establish the role of LAG-3 and CD-155 expressions in predicting the outcomes of nivolumab treatment. Both molecules have a key role in antitumor immunity mechanisms and further researches are needed.
Legal entity responsible for the study
The authors.
Funding
Hacettepe University Scientific Research Projects Coordination Unit.
Disclosure
M. Erman: Financial Interests, Personal and Institutional, Invited Speaker: Astellas, Deva, Abdi Ibrahim, Nobel, Roche, Bristol Myers Squibb, Merck Sharp & Dohme, Merck, Pfizer, Novartis, Eczacibasi; Financial Interests, Personal and Institutional, Funding: Roche, Merck, Sharp Dohme, Incyte, Bristol Myers Squibb, BeiGene, Novartis, Pfizer, Boehringer Ingelheim, AstraZeneca, Regeneron. All other authors have declared no conflicts of interest.