Univariate and multivariate analyses for OS using Cox proportional hazards regression model in ICI rechallenge cohort
| Characteristics | Univariate analysis | Multivariate analysis | ||
|---|---|---|---|---|
| HR (95% CI) | P | HR (95% CI) | P | |
| Age | 0.98 (0.95–1.02) | 0.264 | - | - |
| Gender (male vs. female) | 0.77 (0.32–2.13) | 0.581 | - | - |
| BMI | 0.96 (0.87–1.04) | 0.350 | - | - |
| ECOG PS at ICI rechallenge (2 vs. 0/1) | 6.84 (2.87–13.68) | < 0.001 | 4.51 (1.30–15.89) | 0.037 |
| Smoking (never vs. ever) | 3.28 (1.45–7.56) | 0.004 | 1.28 (0.37–4.28) | 0.686 |
| Histology (squamous vs. non-squamous) | 1.84 (0.73–4.37) | 0.234 | - | - |
| PD-L1 expression (< 50% vs. ≥ 50%) | 2.72 (0.94–11.52) | 0.106 | - | - |
| Liver metastasis at ICI rechallenge (yes vs. no) | 1.66 (0.67–3.80) | 0.241 | - | - |
| Brain metastasis at ICI rechallenge (yes vs. no) | 1.44 (0.34–4.31) | 0.560 | - | - |
| Bone metastasis at ICI rechallenge (yes vs. no) | 2.39 (0.85–5.84) | 0.071 | - | - |
| Metastatic sites at ICI rechallenge (< 2 vs. ≥ 2) | 2.07 (0.68–5.23) | 0.151 | - | - |
| Line of initial ICI therapy (1 vs. 2) | 0.43 (0.07–1.45) | 0.249 | - | - |
| Initial ICI regimen (monotherapy vs. combination chemotherapy) | 0.67 (0.22–1.68) | 0.430 | - | - |
| Best overall response to initial ICI therapy (CR/PR vs. SD/PD) | 0.06 (0.01–0.22) | 0.002 | 0.19 (0.04–0.80) | 0.028 |
| Duration of initial ICI therapy (≥ 1 year vs. < 1 year) | 0.56 (0.22–1.29) | 0.196 | - | - |
| irAEs at initial ICI therapy (yes vs. no) | 0.60 (0.24–1.37) | 0.243 | - | - |
| Treatment between two lines of ICI (yes vs. no) | 1.28 (0.57–2.98) | 0.553 | - | - |
| ICI rechallenge regimen (monotherapy vs. combination chemotherapy) | 0.66 (0.15–1.92) | 0.500 | - | - |
| Type of ICIs in rechallenge settings [anti-PD-L1 (atezolizumab) vs. anti-PD-1 (pembrolizumab/nivolumab)] | 1.13 (0.44–3.00) | 0.794 | - | - |
| Rechallenge with the same ICI (no vs. yes) | 0.83 (0.36–1.87) | 0.663 | - | - |
| Line of ICI rechallenge therapy (< 4 vs. ≥ 4) | 0.48 (0.19–1.48) | 0.158 | - | - |
| Baseline NLR at ICI rechallenge (≥ 3.8 vs. < 3.8) | 6.59 (2.71–12.92) | < 0.001 | 6.80 (1.95–13.84) | 0.003 |
| irAEs at ICI rechallenge (yes vs. no) | 0.69 (0.25–1.66) | 0.436 | - | - |
BMI: body mass index; ECOG PS: Eastern Cooperative Oncology Group Performance Status; NLR: neutrophil-to-lymphocyte ratio; irAEs: immune-related adverse events; HR: hazard ratio; OS: overall survival; SD: stable disease; PD: progressive disease; CR: complete response; PR: partial response; PD-L1: programmed cell death-ligand 1; ICI: immune checkpoint inhibitor; PD-1: programmed cell death protein 1
