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
| 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 | – | – |