Univariate and multivariate analyses for PFS 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 (0.96–1.06) | 0.181 | - | - |
| Gender (male vs. female) | 0.65 (0.33–1.43) | 0.254 | - | - |
| BMI | 0.96 (0.89–1.03) | 0.265 | - | - |
| ECOG PS at ICI rechallenge (2 vs. 0/1) | 5.31 (2.46–11.45) | < 0.001 | 3.41 (1.28–9.05) | 0.013 |
| Smoking (never vs. ever) | 1.79 (0.91–3.44) | 0.084 | - | - |
| Histology (squamous vs. non-squamous) | 0.62 (0.32–1.22) | 0.169 | - | - |
| PD-L1 expression (< 50% vs. ≥ 50%) | 1.30 (0.59–2.62) | 0.481 | - | - |
| Liver metastasis at ICI rechallenge (yes vs. no) | 1.03 (0.47–2.06) | 0.941 | - | - |
| Brain metastasis at ICI rechallenge (yes vs. no) | 2.06 (0.60–5.38) | 0.182 | - | - |
| Bone metastasis at ICI rechallenge (yes vs. no) | 2.33 (1.02–4.81) | 0.030 | 1.59 (0.58–4.19) | 0.356 |
| Metastatic sites at ICI rechallenge (< 2 vs. ≥ 2) | 1.83 (0.74–3.94) | 0.152 | - | - |
| Line of initial ICI therapy (1 vs. 2) | 0.64 (0.22–1.52) | 0.362 | - | - |
| Initial ICI regimen (monotherapy vs. combination chemotherapy) | 0.83 (0.37–1.71) | 0.636 | - | - |
| Best overall response to initial ICI therapy (CR/PR vs. SD/PD) | 0.41 (0.19–0.89) | 0.026 | 0.34 (0.16–0.78) | 0.014 |
| Duration of initial ICI therapy (≥ 1 year vs. < 1 year) | 0.56 (0.26–1.11) | 0.107 | - | - |
| irAEs at initial ICI therapy (yes vs. no) | 1.11 (0.57–2.12) | 0.758 | - | - |
| Treatment between two lines of ICI (yes vs. no) | 1.58 (0.83–3.09) | 0.169 | - | - |
| ICI rechallenge regimen (monotherapy vs. combination chemotherapy) | 0.77 (0.34–2.04) | 0.552 | - | - |
| Type of ICIs in rechallenge settings [anti-PD-L1 (atezolizumab) vs. anti-PD-1 (pembrolizumab/nivolumab)] | 1.13 (0.55–2.40) | 0.741 | - | - |
| Rechallenge with the same ICI (no vs. yes) | 0.99 (0.52–1.94) | 0.982 | - | - |
| Line of ICI rechallenge therapy (< 4 vs. ≥ 4) | 0.58 (0.28–1.31) | 0.158 | - | - |
| Baseline NLR at ICI rechallenge (≥ 3.8 vs. < 3.8) | 6.76 (3.17–15.48) | < 0.001 | 5.89 (2.25–16.20) | 0.001 |
| irAEs at ICI rechallenge (yes vs. no) | 1.08 (0.52–2.11) | 0.830 | - | - |
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; SD: stable disease; PD: progressive disease; CR: complete response; PR: partial response; PFS: progression-free survival; PD-L1: programmed cell death-ligand 1; ICI: immune checkpoint inhibitor; PD-1: programmed cell death protein 1
