Tumor metabolic volume by 18F-FDG-PET as a prognostic predictor of first-line pembrolizumab for NSCLC patients with PD-L1 ≥ 50%

Abstract

There is a lack of markers for predicting favorable outcomes after pembrolizumab therapy in patients with non-small cell lung cancer (NSCLC) with programmed death ligand-1 (PD-L1) expression ≥ 50%. This retrospective study examined the prognostic significance of 2-deoxy-2-[18F] fluoro-d-glucose (18F-FDG) uptake as a predictive marker of first-line pembrolizumab. Forty-eight patients with previously untreated NSCLC and PD-L1 expression levels ≥ 50% who underwent 18F-FDG-positron emission tomography (PET) just before administration of pembrolizumab monotherapy were eligible and underwent assessment of metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum of standardized uptake value (SUVmax) on 18F-FDG uptake. The objective response rate, median progression-free survival, and median overall survival were 51.1%, 7.1 months, and 18.6 months, respectively. In univariate survival analyses, high MTV was barely a significant prognostic predictor and was confirmed as an independent factor linked to worse outcomes in multivariate analysis, predominantly in patients with a histological diagnosis of adenocarcinoma. A high MTV was significantly associated with distant metastases (especially bone metastasis), C-reactive protein (CRP) level, and PD-L1 expression ≥ 75%. Metabolic tumor activity assessed as MTV from 18F-FDG uptake predicted the prognosis after first-line pembrolizumab treatment in patients with NSCLC and PD-L1 expression ≥ 50%, especially for adenocarcinoma.

First-line immunotherapy in non-small cell lung cancer patients with poor performance status: a systematic review and meta-analysis

“…When compared to PS 0-1 patients, poor PS ones had frequently worse response and DCRs, and in many cases the difference was statistically significant (Table 5). Pooling the data, 491 and 210 PS ≥2 patients were evaluated for ORR [seven studies (28,29,40,41,45,46,51)] and DCR [five studies (29,36,37,40,41)], respectively (Figures S1,S2). Disease responses were observed in 30.9% of the cases [95% CI: 22.5-40.0%] and 41.5% of the patient achieved disease control (95% CI: 27.1-56.9%) (Figure 2).…”

“…Across studies, 1,262 ECOG PS 0-1 patients in five studies were evaluated for disease response (28,40,45,46,51) and ORR was 55.2% (95% CI: 42.8-67.2%) (Figure 2C; Figure S3). DCR data was obtained for 185 patients in four studies (36,37,40,51) and occurred in 71.5% of the cases (95% CI: 56.0-84.7%) (Figure 2D; Figure S2). Heterogeneity was significant for both ORR (I 2 =92.6%, 95% CI: 85.6-95.1%; P<0.0001) and DCR (I 2 =79.45%, 95% 45.28-92.28%; P=0.0022) (Figures S3,S4).…”

Molecular Imaging and the PD-L1 Pathway: From Bench to Clinic

“…A metabolic score derived from combined assessment of pretreatment MTV and the neutrophil-to-lymphocyte ratio may provide a more accurate prediction of outcome than either of these factors alone ( 47 , 48 ). Furthermore, in patients with NSCLC, the maximal standard uptake value (SUV) of 18 F-FDG has been reported to be positively associated with PD-L1 expression ( 49 , 50 ), and high 18 F-FDG MTV is associated with PD-L1 expression ≥75% ( 48 ). However, 18 F-FDG PET imaging, like computed tomography (CT), can show pseudoprogression (an early increase in tumor volume and FDG uptake on imaging with a subsequent favorable response to ICI therapy) ( 51 , 52 ).…”

“…For example, lower total lesion glycolysis and metabolic tumor volume (MTV), as determined in patients with NSCLC using 18 F-FDG PET, have been shown to be prognostic and predictive of response and longer overall survival following nivolumab or pembrolizumab monotherapy (43)(44)(45)(46). A metabolic score derived from combined assessment of pretreatment MTV and the neutrophil-to-lymphocyte ratio may provide a more accurate prediction of outcome than either of these factors alone (47,48). Furthermore, in patients with NSCLC, the maximal standard uptake value (SUV) of 18 F-FDG has been reported to be positively associated with PD-L1 expression (49,50), and high 18 F-FDG MTV is associated with PD-L1 expression ≥75% (48).…”

First-Line Pembrolizumab Therapy of Non-Small Cell Lung Cancer: Baseline Metabolic Biomarkers Predict Outcomes

“…[4,16,17] Concerning NSCLC treated with chemotherapy or ICI, especially volume-based PET/CT variables like total (whole-body) metabolic tumor volume (MTV) and total lesion glycolysis (TLG) have been shown predictive properties in terms of therapy response and survival. [18][19][20][21][22][23][24][25][26] Of interest, the combination of the quantitative PET/CT biomarker MTV and the blood-based biomarker derived neutrophil to lymphocyte ratio (DNLR) had predictive impact in NSCLC patients receiving ICI. [26][27][28] Similar to DNLR, also PET/CT allows an estimation of the activity of lymphatic tissues, as usually expressed by the bone marrow to liver ratio (BLR) or the spleen to liver ratio (SLR).…”