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Table 1 Prognostic and predictive factors in A) clinical findings, B) laboratory values and C) immunohistochemistry and genetics for ICI treatment in NSCLC discussed in this review in more detail. Level of evidence is given for every marker. Sequence of studies as appearance in the review. n.s., not significant; + statistically significant positive prognostic/predictive factor; − statistically significant negative prognostic/predictive factor

From: Clinically relevant prognostic and predictive markers for immune-checkpoint-inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC)

Authors Year ICI n Biomarker Level of evidence PFS OS
Clinical findings
 Conforti et al. [26] 2018 ICI single agent therapy 11,351 male gender 2A NS +
 Conforti et al. [27] 2019 PD-L1/PD-1 inhibitor + chemotherapy 4923 female gender 2A + +
 Kawachi et al. [28] 2020 pembrolizumab 213 pleural effusion 2B NS
ECOG PS < 2 2B + NS
 Naqash et al. [29] 2020 nivolumab 531 irAE 2B + +
ECOG PS < 2 2B + +
ICI duration > 3 months 2B + +
 Dall’Olio et al. [30] 2020 immunotherapy 3600 ECOG PS ≥ 2 2A
 Cortellini et al. [31] 2020 PD-1/PD-L1 inhibitors 1070 BMI ≥ 25 kg/m^2 3B + +
 Shepshelovich et al. [32] 2019 various assessments 25,439 BMI ≥ 40 / <  18,5 kg/m^2 2A NS
 Magri et al. [33] 2019 nivolumab 46 weight loss before treatment > 5% 2B NS
 Kang et al. [34] 2018 PD-1/PD-L1 inhibitors 51 pleural or pericardial metastasis 3B NS
 Adachi et al. [35] 2020 nivolumab 296 driver mutation positivity 3B NS
CRP ≥ 1 mg/dL 3B NS
liver metastasis 3B NS
pleural effusion 3B NS
ALI ≥ 18 3B + NS
baseline steroid use 3B NS
 Reck et al. [36] 2019 ABCP 1202 liver metastasis 1A + +
 Sridhar et al. [37] 2019 Durvalumab 569 liver metastasis 1A
 Scott et al. [38] 2018 nivolumab 210 baseline steroid use 3B NS
 Fuca et al. [39] 2019 PD-1/PD-L1 inhibitors 151 baseline steroid use 3B
 Arbour et al. [40] 2018 PD-1/PD-L1 inhibitors 640 baseline steroid use 3B
 Routy et al. [41] 2018 PD-1/PD-L1 inhibitors 379 antibiotic use (60 days before thx) 2B
 Derosa et al. [42] 2018 PD-1/PD-L1 inhibitors 239 antibiotic use (30 days before thx) 3B NS
 Ahmed et al. [43] 2018 PD-1/PD-L1 inhibitors 60 broad spectrum antibiotics 2B NS
 Chalabi et al. [44] 2020 atezolizumab + docetaxel 1512 antibiotic use 1A NS
 Hakozaki et al. [45] 2020 nivolumab, pembrolizumab or atezolizumab 90 decreased Ruminococcaceae UCG 13 and Agathobacter 2B
Laboratory values
 Cao et al. [46] 2018 nivolumab 1225 NLR ≥ 5 3A
 Zhang et al. [47] 2020 ICI therapy 2nd-line 74 NLR ≥ 3 3B NS NS
 Iivanainen et al. [48] 2019 PD-1/PD-L1 inhibitors 160 NLR > 2,65 2B
CRP ≥ 10 mg/mL 2B
 Liu et al. [49] 2019 nivolumab 44 NLR ≤ 3.07 3B + +
SII ≤ 603.5 3B + +
PLR ≤ 144 3B + +
 Mezquita et al. [50] 2018 PD-1/PD-L1 inhibitors 628 positive LIPI 2B NS
LDH > UNL 2B NS +
 Passaro et al. [51] 2020 nivolumab 53 Gr-MDSC < 6 cells/μl 2B + +
NC < 5840/μl 2B + +
eosinophils > 90/μl 2B + +
NLR < 3 2B + +
 Tanizaki et al. [52] 2018 nivolumab 134 ALC > 1000/μ 3B + NS
AEC > 150/μL 3B + NS
ANC > 7500/μL 3B
 Zhang et al. [53] 2019 PD-1/PD-L1 inhibitors 1136 LDH > UNL 3A + +
 Naqash et al. [54] 2018 nivolumab 87 CRP > 50 mg/L 2B NS
NLR > 6,5 2B NS
PNI < 31,5 2B NS
Immunohistochemistry and genetic parameters
 Okuma et al. [55] 2018 nivolumab 39 sPD-L1 > 3357 ng/mL 2B NS +
 Costantini et al. [56] 2018 nivolumab 43 low sPD-L1 2B + +
 Shibaki et al. [57] 2020 nivolumab, pembrolizumab 235 low serum VEGF 3B + +
 Wang et al. [58] 2019 PD-1/PD-L1 inhibitors 98 bTMB > 6 3B + NS
 Rizvi et al. [59] 2020 durvalumab vs. durvalumab + tremelimumab vs. chemo 1118 bTMB ≥20 mut/mb 1B NS +
 Paz-Ares et al. [60] 2019 pembrolizumab + chemo vs. chemo 605 tTMB 1A NS NS
 Herbst et al. [61] 2019 pembrolizumab vs. platinum-based chemo 1274 KRAS & pembrolizumab 1B + +
 Gadgeel et al. [62] 2019 pembrolizumab+premetrexed+platinum vs. placebo+premetrexed+platinum 616 KRAS & pembrolizumab +chemo 1B + +
 Skoulidis et al. [63] 2018 PD-1/PD-L1 inhibitors 1208 STK11/LKB1 2B
 Arbour et al. [64] 2019 ICI inhibitors vs. chemotherapy 330 KEAP1/NFE2L2 2B NS
 Cho et al. [65] 2020 pembrolizumab vs. platinum-based chemo 1274 STK11 or KEAP1 1B NS NS
 Bratman et al. [66] 2020 pembrolizumab 94 low baseline ct-DNA concentration 2A + +
 Zulato et al. [67] 2020 ICI therapy 34 new KRAS mutation becoming apparent after 3–4 weeks 2B