18F-FDG PET–derived parameter total lesion glycolisis (TLG) as a tool to stratify patients (pts) with advanced non–small cell lung cancer (aNSCLC) treated with immunotherapy.
Authors: Dall'Olio Filippo Gustavo , Garcia Camilo , Ambrosini Valentina , Tagliamento Marco , Helissey Carole , Velasco Monica , Bettayeb Mohamed Aymen , Aldea Mihaela , Conci Nicole , Bauckneht Matteo , Bonardel Gerald , Argalia Giulia , Soldato Davide , Cella Eugenia , Remon Masip Jordi , Planchard David , Balleyguier Corinne , Ardizzoni Andrea , Barlesi Fabrice , Besse Benjamin 
Published: June 2022

9062 Background: Upfront Immune Checkpoint Blockers (ICB) alone or in combination with chemotherapy (CT) have become the backbone treatment of non-oncogene addicted aNSCLC. PD-L1 remains the only predictive biomarker, but additional biomarkers are mandatory to better discriminate the population more suitable for the combination approach (CT-ICB). We hypothesized that TLG, a parameter that measure tumor burden and metabolic activity, may help to select the optimal first-line regimen. Methods: We performed a multicentric (n = 5) retrospective study including pts treated either with ICB alone, CT-ICB or CT alone. Overall survival (OS) and progression-free survival (PFS) were estimated with Kaplan-Meier analysis. Hazard ratios (HR) were calculated using multivariate Cox proportional Hazard models adjusting for relevant covariates (neutrophil/lymphocyte ratio, ECOG PS, liver, bone metastases). TLG was calculated on PET scans as the product of metabolic tumor volume (with a threshold of 42% of SUV max) and SUV mean. Results: 250 pts with aNSCLC initiated first-line treatment (94 ICB, 102 CT-ICB and an hystorical control group of 54 CT) within 42 days from PET. Median follow up was 22 months for ICB, 16 for CT-ICB and 47 for CT. 170 pts were male (68%), 210 had non-squamous histology (84%), 110 (44%)and 38 (15%) had bone and liver metastasis, respectively. On the 194 pts with PD-L1 status available: 20%, 29% and 50% had PD-L1 < 1%, 1-49% and > 50%, respectively. No correlation was seen between PD-L1 and TLG. Presence of liver metastases (13% vs 2%) and ECOG PS > 1 (16% vs 3%) were associated with elevated TLG. PFS correlated with TLG, with longer median PFS in the lower quartile (TLG < 380) either with ICB (12.4 vs 4.7 months, HR 1.9, 95% CI1.1 – 3.35, p 0.025) and CT-ICB (17.9 vs 7.3, HR 1.9, 95% CI1.1 – 3.7, p 0.032) but not with CT (4.2 vs 3.5, p 0.986), whereas OS was correlated with TLG < 380 in all 3 groups. The risk of progression under ICB was lower in tumors with TLG < 380 (15% vs.29%, p = 0.02), but no difference was seen in other 2 groups. In PD-L1 ≥50% pts with elevated TLG, treatment with CT-ICB (n = 20) increased the PFS respect with ICB (n = 55) (10.7 vs 3.9, HR 0.54, 95% CI 0.29 – 0.99, p = 0.048).The analysis was underpowered to find a difference in OS (HR 0.49, 95% CI 0.21 - 1.12, p = 0.092). Conclusions: TLG retains a prognostic validity in aNSCLC identifying pts with an increased rate of early progression on ICB, who may benefit from CT-ICB. Further analyses are required to compare CT-ICB and ICB in PD-L1 ≥50% according to TLG. Enrollement from other centers is ongoing, an update will be presented.