Abstract 993P
Background
A metabolic change towards a high glycolytic pattern is considered one of the hallmarks of cancers and has been implicated in immune evasion. We evaluated whether the glycolytic tumor burden accessed by a pretreatment 18F-FDG PET/CT (PET) impacts the response and survival in metastatic NSCLC patients (pts) undergoing immune checkpoint inhibitors (ICI). We also evaluated whether the use of metformin is associated with modifications in the glycolytic tumor burden in this group of pts.
Methods
This is a retrospective single-center study, which included NSCLC pts for whom a baseline PET was performed prior to ICI treatment. Clinical data retrieval and analysis of PET were each performed by independent reviewers. Glycolytic parameters were calculated as SUV (maximum standardized uptake value), wMTV (whole metabolic tumor value), and wTLG (whole total lesion glycolysis). Best response rates were categorized according to RECIST 1.1 criteria. Subgroups were defined as having either high or low glycolytic tumor burden according to SUV, wMTV and wTLG cut-offs calculated upon ROC curves depiction. Survival curves were estimated using Kaplan Meier method and compared by log-rank.
Results
Ninety-eight pts were included for analysis. Among all PET glycolytic parameters, there was a statistic significant correlation between glycolytic tumor burden (low vs high) and response (responder vs non-responder): p .001 for SUV, p .003 for wMTV and p < .001 for wTLG (Mann-Whitney test). In addition, no pts with a low wTLG (146.9) developed progressive disease. Moreover, a low glycolytic tumor burden was significant correlated with improved overall survival (p .014 for SUV, p .001 for wMTV and p < .001 for TLG, log-rank test). Among 15 pts under metformin, a significant lower glycolytic tumor burden was found, in addition to a better rate of response and overall survival.
Conclusions
In NSCLC, glycolytic tumor burden accessed by a pretreatment 18F-FDG PET/CT may be a promising biomarker to tailor benefit from ICI. Furthermore, modulation of the tumor metabolism with metformin may contribute to enhance ICI efficacy and warrants further investigations.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
G. de Castro Jr.: Other, Personal, Invited Speaker: Amgen; Other, Personal, Advisory Board: Amgen; Other, Personal, Invited Speaker: AstraZeneca; Other, Personal, Advisory Board: AstraZeneca; Other, Personal, Invited Speaker: Bayer; Other, Personal, Advisory Board: Bayer; Other, Personal, Invited Speaker: Boehringer Ingelheim; Other, Personal, Advisory Board: Boehringer Ingelheim; Other, Personal, Invited Speaker: Bristol-Myers Squibb; Other, Personal, Advisory Board: Bristol-Myers Squibb; Other, Personal, Advisory Board: Janssen; Other, Personal, Invited Speaker: Janssen; Other, Personal, Advisory Board: Libbs; Other, Personal, Advisory Board: Lilly; Other, Personal, Invited Speaker: Merck Serono; Other, Personal, Advisory Board: Merck Serono; Other, Personal, Invited Speaker: Merck Sharp & Dohme; Other, Personal, Advisory Board: Merck Sharp & Dohme; Other, Personal, Invited Speaker: Novartis; Other, Personal, Advisory Board: Novartis; Other, Personal, Invited Speaker: Pfizer; Other, Personal, Advisory Board: Pfizer; Other, Personal, Invited Speaker: Roche; Other, Personal, Advisory Board: Roche; Other, Personal, Invited Speaker: Teva Pharmaceuticals; Other, Personal, Advisory Board: Teva Pharmaceuticals; Other, Personal, Invited Speaker: Yuhan; Non-Financial Interests, Personal, Principal Investigator: Amgen; Non-Financial Interests, Institutional, Principal Investigator: AstraZeneca; Non-Financial Interests, Institutional, Principal Investigator: GlaxoSmithKline; Non-Financial Interests, Institutional, Principal Investigator: Merck Serono; Non-Financial Interests, Institutional, Principal Investigator: Merck Sharp & Dohme; Non-Financial Interests, Institutional, Principal Investigator: Novartis; Non-Financial Interests, Institutional, Principal Investigator: Roche. All other authors have declared no conflicts of interest.