Table 1.
The main characteristics of studies included in this meta-analysis
| ID | Country | Cancer type | ICIs treatment | ICIs line of treatments | Concomitant medications | Sample size (Y/N) |
Outcome | Median PFS (Users vs non-users) (Month) |
Median OS (Users vs non-users) (Month) |
Analysis model | NOS |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Afzal2019 | US | NSCLC | Pembrolizumab Nivolumab Atezolizumab |
First-line Second-line Third-line | Metformin | 21/29 | PFS/OS | 4 vs 3 | 11.5 vs 7.6 | Univariate | 6 |
| Afzal2018 | US | Melanoma | Pembrolizumab Nivolumab Ipilimumab + Nivolumab Ipilimumab |
First-line | Metformin | 33/22 | PFS/OS | 19.8 vs 5 | 46.7 vs 28 | Univariate | 6 |
| Buti2021 | Italy | NSCLC Melanoma RCC Others |
PD-1 inhibitors PD-L1 inhibitors CTLA-4 inhibitors |
First-line Second-line Third-line |
Statin Low-dose aspirin Metformin |
56/161 43/174 17/200 |
PFS/OS | 3.6 vs 3.6 3.2 vs 3.6 3.8 vs 3.6 |
12.4 vs 8.4 8.9 vs 8 12.6 vs 8.7 |
Univariate | 6 |
| Cortellini2020 | Italy | NSCLC Melanoma RCC Others |
Pembrolizumab Nivolumab Atezolizumab Others |
First Non- first |
Statin NSAIDs Low-dose aspirin Metformin Beta blockers |
192/820 59/953 189/823 114/868 114/898 |
PFS/OS | NA | NA | Multivariate | 7 |
| Cantini 2021 | Italy | NSCLC MPM |
Nivolumab Pembrolizumab |
Second-line Third-line | Statin | 67/186 | PFS/OS | 7.8 vs 3.6 6.7 vs 2.3 |
13.1 vs 10.1 NR vs 6 |
Multivariate | 6 |
| Failing2016 | US | Melanoma | Ipilimumab | First-line | Statin NSAIDs Low-dose aspirin Metformin |
40/119 31/128 38/121 12/147 |
PFS/OS | NA | NA | Multivariate | 6 |
| Kanai2021 | Japan | NSCLC | Atezolizumab Nivolumab Pembrolizumab |
Second-line Third-line | NSAIDs | 65/133 | PFS/OS | 3.45 vs 3.94 | 7.85 vs 15.11 | Univariate | 5 |
| Gaucher2021 | France | Lung Melanoma Renal and urothelial Head and neck Others |
Nivolumab Pembrolizumab Ipilimumab Nivolumab + Ipilimumab |
First-line Second-line Third-line |
Metformin | 17/355 | OS | NA | NR vs 15.62 | Multivariate | 6 |
| Michael 2020 | US | NSCLC | Nivolumab Pembrolizumab Atezolizumab |
Second-line Third-line | Beta-blockers | 28/81 | PFS/OS | 10.3 vs 5 | 21.5 vs13.3 | Univariate | 5 |
| Nichetti 2020 | Italy | NSCLC | PD-1 inhibitors PD-L1 inhibitors PD-L1 + CTLA-4 inhibitors |
First-line Second-line Third-line |
Low-dose aspirin | 61/156 | PFS | 6.59 vs 3.18 | NA | Univariate | 5 |
| Svaton2020 | Czech | NSCLC | Nivolumab | First-line Second-line Third-line or higher |
Statin NSAIDs Metformin |
31/193 45/178 18/206 |
PFS/OS | 7.2 vs 5.4 6.9 vs 5.3 3.3 vs 6 |
16.8 vs 12.9 16.8 vs 12.8 10.6 vs 13.1 |
Multivariate | 6 |
| Wang D.Y 2020 | Mixed | Melanoma | Nivolumab Pembrolizumab | First-line | NSAIDs Low-dose aspirin Metformin Beta-blocker |
122/208 47/283 34/296 65/265 |
PFS/OS | 8.5 vs 5.2 NA 11.1 vs 5.6 11.2 vs 5.5 |
25.7 vs 27.3 NA 27.6 vs 26.0 27.8 vs 25.8 |
Multivariate/Univariate | 5 |
| Wang S.J 2020* | US | Melanoma NSCLC |
PD-1 inhibitors PD-L1 inhibitors CTLA-4 inhibitors |
NA | NSAIDs | 32/58 20/17 |
OS | NA | 25.44 vs22.08 37.68 vs 14.28 |
Multivariate | 6 |
*:Wang S.J 2020 study included 2 cohorts which are melanoma patients and NSCLC patients, respectively.
Abbreviations: OS, overall survival; PFS, progression-free survival; NSCLC, non-small cell lung cancer; NSAIDS, non-steroidal anti- inflammatory drugs; MPM, malignant pleural mesothelioma; RCC, renal cell carcinoma; NA, not available; NR, not reached.