Table 2.
Univariate and multivariate analysis of factors associated with progression-free and overall survival following immune checkpoint-inhibitor-based therapies
| Progression-Free Survival | Overall Survival | |||||
|---|---|---|---|---|---|---|
| HR | 95% CI | p-value | HR | 95% CI | p-value | |
|
Univariate Models
(n = 62) | ||||||
| High TMB | 0.46 | 0.22–0.95 | 0.04 | 0.48 | 0.22–1.05 | 0.07 |
| PTEN alteration | 2.04 | 1.15–3.63 | 0.01 | 2.19 | 1.16–4.13 | 0.02 |
| ECOG PS | 1.72 | 0.58–3.05 | 0.06 | 3.24 | 1.74–6.04 | 0.0002 |
| Previous lines of therapy | 1.57 | 0.91–2.71 | 0.11 | 1.39 | 0.75–2.56 | 0.30 |
| Regimen | 1.31 | 0.69–2.49 | 0.41 | 1.14 | 0.57–2.26 | 0.72 |
| Visceral metastases | 1.10 | 0.59–2.06 | 0.77 | 1.11 | 0.56–2.20 | 0.77 |
|
High TMB Multivariate Model
(n = 62) | ||||||
| High TMB | 0.42 | 0.19–0.93 | 0.03 | 0.54 | 0.23–1.26 | 0.15 |
| ECOG PS | 1.64 | 0.89–3.00 | 0.11 | 2.93 | 1.53–5.63 | 0.001 |
| Previous lines of therapy | 1.57 | 0.89–2.76 | 0.12 | 1.29 | 0.68–2.45 | 0.43 |
| Regimen | 1.83 | 0.90–3.73 | 0.10 | 1.54 | 0.71–3.35 | 0.27 |
| Visceral metastases | 1.50 | 0.79–2.86 | 0.22 | 1.35 | 0.65–2.82 | 0.42 |
|
PTEN Alteration Multivariate Model
(n = 62) | ||||||
| PTEN alteration | 2.71 | 1.44–5.10 | 0.002 | 3.26 | 1.59–6.68 | 0.001 |
| ECOG PS | 1.98 | 1.08–3.62 | 0.03 | 3.84 | 1.99–7.39 | 0.00006 |
| Previous lines of therapy | 1.83 | 1.02–3.29 | 0.04 | 1.57 | 0.81–3.06 | 0.18 |
| Regimen | 1.84 | 0.90–3.74 | 0.09 | 1.69 | 0.78–3.62 | 0.18 |
| Visceral metastases | 1.21 | 0.64–2.30 | 0.56 | 1.05 | 0.52–2.14 | 0.88 |
|
High TMB and PTEN Alteration Multivariate Model
(n = 62) | ||||||
| High TMB | 0.37 | 0.17–0.80 | 0.01 | 0.48 | 0.20–1.14 | 0.10 |
| PTEN alteration | 3.07 | 1.62–5.81 | 0.0006 | 3.44 | 1.67–7.07 | 0.0008 |
| ECOG PS | 1.67 | 0.91–3.05 | 0.10 | 3.34 | 1.72–6.49 | 0.0004 |
| Previous lines of therapy | 1.79 | 1.00–3.21 | 0.05 | 1.48 | 0.76–2.87 | 0.25 |
| Regimen | 2.38 | 1.15–4.96 | 0.02 | 2.05 | 0.92–4.55 | 0.08 |
| Visceral metastases | 1.45 | 0.75–2.78 | 0.27 | 1.28 | 0.61–2.67 | 0.52 |
|
High TMB, PTEN Alteration, and PD-L1 Multivariate Model
(n = 37) | ||||||
| High TMB | 0.37 | 0.15–0.91 | 0.03 | 0.42 | 0.16–1.11 | 0.08 |
| PTEN alteration | 2.82 | 1.16–6.85 | 0.02 | 2.93 | 1.14–7.53 | 0.03 |
| PD-L1 | 0.78 | 0.31–1.93 | 0.59 | 1.28 | 0.48–3.43 | 0.63 |
| ECOG PS | 1.16 | 0.47–2.87 | 0.74 | 2.27 | 0.90–5.73 | 0.08 |
| Previous lines of therapy | 1.41 | 0.62–3.18 | 0.41 | 1.39 | 0.59–3.30 | 0.45 |
| Regimen | 1.18 | 0.41–3.42 | 0.76 | 1.70 | 0.58–4.97 | 0.33 |
| Visceral metastases | 0.71 | 0.27–1.88 | 0.50 | 1.00 | 0.39–2.59 | 0.99 |
High TMB: ≥ 10 mutations/megabase vs. < 10 mutations/megabase; PTEN alteration (nonsynonymous mutation or 1 or 2 copy deletion): present vs. absent; PD-L1: positive vs. negative; ECOG PS: ≥ 1 vs. 0; Previous lines of therapy: ≥ 1 vs. 0; Regimen: monotherapy vs. combination therapy; Visceral metastases: present vs. absent.
Abbreviations: CI: confidence interval; ECOG-PS: Eastern Cooperative Oncology Group performance status; HR: hazard ratio; TMB: tumor mutational burden.