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

SIMPLE SUMMARY: Positron-emission tomography/computed tomography (PET/CT) is used for staging of non-small cell lung cancer (NSCLC) and can help to estimate prognosis in patients treated with immune checkpoint inhibitor (ICI) therapy. Most available data in that field were derived from cohorts treated in higher therapy lines using ICI monotherapy with different drugs. Currently, however, most advanced NSCLC patients receive first-line ICI treatment, often in combination with cytotoxic chemotherapy. We evaluated prognostic PET/CT biomarkers in 85 patients receiving first-line ICI, 70 (82%) of them as a chemotherapy–ICI combination. We found that patients with a higher metabolically active tumor volume (MTV) had a significantly poorer survival and lower radiological response rate. In patients with high MTV, a concomitantly low bone marrow to liver ratio indicated a better prognosis. Our results demonstrate that PET/CT-derived biomarkers can aid therapeutic decision-making in ICI-treated NSCLC. ABSTRACT: Quantitative biomarkers derived from positron-emission tomography/computed tomography (PET/CT) have been suggested as prognostic variables in immune-checkpoint inhibitor (ICI) treated non-small cell lung cancer (NSCLC). As such, data for first-line ICI therapy and especially for chemotherapy–ICI combinations are still scarce, we retrospectively evaluated baseline (18)F-FDG-PET/CT of 85 consecutive patients receiving first-line pembrolizumab with chemotherapy (n = 70) or as monotherapy (n = 15). Maximum and mean standardized uptake value, total metabolic tumor volume (MTV), total lesion glycolysis, bone marrow-/and spleen to liver ratio (BLR/SLR) were calculated. Kaplan–Meier analyses and Cox regression models were used to assess progression-free/overall survival (PFS/OS) and their determinant variables. Median follow-up was 12 months (M; 95% confidence interval 10–14). Multivariate selection for PFS/OS revealed MTV as most relevant PET/CT biomarker (p < 0.001). Median PFS/OS were significantly longer in patients with MTV ≤ 70 mL vs. >70 mL (PFS: 10 M (4–16) vs. 4 M (3–5), p = 0.001; OS: not reached vs. 10 M (5–15), p = 0.004). Disease control rate was 81% vs. 53% for MTV ≤/> 70 mL (p = 0.007). BLR ≤ 1.06 vs. >1.06 was associated with better outcomes (PFS: 8 M (4–13) vs. 4 M (3–6), p = 0.034; OS: 19 M (12-/) vs. 6 M (4–12), p = 0.005). In patients with MTV > 70 mL, concomitant BLR ≤ 1.06 indicated a better prognosis. Higher MTV is associated with inferior PFS/OS in first-line ICI-treated NSCLC, with BLR allowing additional risk stratification.