FDG-PET biomarkers associated with long-term benefit from first-line immunotherapy in patients with advanced non-small cell lung cancer.

Objective: To determine FDG-PET biomarkers associated with long-term benefit (LTB) and survival in advanced non-small cell lung cancer (NSCLC) patients receiving first-line immunotherapy.

Methods: In this multicenter study, we retrospectively analyzed advanced NSCLC patients with a PD-L1 tumor proportion score (TPS) ≥ 50%, who underwent FDG-PET/CT before first-line pembrolizumab, received from August 2017 to September 2019. Parameters extracted were SUVmax, SUVmean, TMTV (total metabolic tumor volume) and TLG (total lesion glycolysis). LTB was defined as objective (complete or partial) response or stable disease as best overall response, maintained for ≥ 12 months. A multivariate prediction model was developed using logistic regression for LTB and Cox models for progression-free survival (PFS) and overall survival (OS).

Results: On the 63 eligible patients, with a median follow-up of 13.4 (range, 1.5-29.1) months, 17 (27%) had LTB. Median PFS and OS were 7.7 months (95%CI 5.0-10.5) and 12.1 months (95%CI 8.6-15.6). In multivariate analyses, high TMTV (> 84cm) and high tumor SUVmean (> 10.1) remained independent factors for predicting LTB (OR 0.2; p = 0.03 and OR 3.7; p = 0.04) and PFS (HR 2.2; p = 0.02 and HR 0.5; p = 0.045). High TMTV was significantly associated with poor OS (HR 3.1; p = 0.03). No association was observed between tumor SUVmax or TLG and clinical outcomes.

Conclusions: In patients with advanced NSCLC and PD-L1 TPS ≥ 50%, baseline low TMTV and high tumor SUVmean correlate with survival and LTB from upfront pembrolizumab. Beyond the initial staging, FDG-PET/CT scan could provide relevant biomarkers associated with clinical outcomes that should be taken into account when considering first-line treatment options.