Table 1.
Baseline characteristics of the studies included in the systematic review and meta-analysis.
| Biomarker | Outcomes | Cut-off value | Study | Region | Type of study | Treatment | Stage | The line of treatment | Sample | Median age (range) |
Male (%) | Median follow-up (months) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EBV DNA | ORR | NR | Yang 2021 (14) | China | Prospective (phase II) |
Camrelizumab | recurrent or metastatic | >2 | 156 | 48 (23–71) | 124 (79.5) | 14.2 (0.7–27.6) |
| EBV DNA | PFS | NR | Yang 2021 (3) | China | Prospective (phase III) |
Camrelizumab combined with chemo (GP) |
recurrent or metastatic | 1 | 134 | 52 (40–58) | 113 (84.0) | 10.2 (IQR:7.7–12.7) |
| EBV DNA | PFS | 10,000IU/mL | Xu J 2022 (20) | China | Prospective (phase II) |
Toripalimab | recurrent or metastatic | >2 | 179 | 46 (22-71) | 148 (82.7) | NR |
| EBV DNA | ORR | 10,000IU/mL | Wang 2021 (9) | China | Prospective (phase II) |
Toripalimab | recurrent or metastatic | >2 | 190 | 46 (22-71) | 158 (83.2) | NR |
| EBV DNA | PFS | 1,500 copies/mL | Hua 2021 (21) | China | Prospective (phase II) |
Toripalimab combined with radiocherapy | recurrence | 1 | 25 | 49(IQR: 43.5–52.5) | 18 (72.0) | 14.6 (IQR: 13.1–16.2) |
| EBV DNA | ORR | 19,000 copies/mL | Even 2021 (22) | France | Prospective (phase II) |
Spartalizumab(PDR001) | recurrent or metastatic | >1 | 82 | 51 (21–74) | 68 (82.9) | NR |
| EBV DNA | ORR, PFS | 30,000 copies/mL | Fang 2018 (23) | China | Prospective (phase I) |
Cohort1: Camrelizumab monotherapy |
recurrent or metastatic | >1 | 93 | 45 (38–52) | 75 (81.0) | 9.9 (IQR:8.1–11.7) |
| EBV DNA | ORR, PFS | 30,000 copies/mL | Fang 2018 (23) | China | Prospective (phase I) |
Cohort2: Camrelizumab combination |
recurrent or metastatic | >1 | 22 | 44 (34–51) | 17 (74.0) | 10.2 (IQR:9.7–10.8) |
| EBV DNA | ORR, PFS | 50,000copies/mL | Xu L 2022 (26) | China | Prospective (phase I/II) |
Camrelizumab or Nivolumab | recurrent or metastatic | ≥1 | 57 | 47(25-72) | 43(75.4) | 5.8 |
| EBV DNA | ORR | 1,000 copies/mL | Shi 2022 (4) | China | Prospective (phase II) |
KL-A167 | recurrent or metastatic | >1 | 132 | 49 (26−68) | 109 (82.6) | 21.7(95%CI: 19.8−22.5) |
| Dynamic EBV DNA | ORR, PFS | 30,000 copies/mL | Fang 2018 (23) | China | Prospective (phase I) |
Cohort1: Camrelizumab monotherapy |
recurrent or metastatic | >1 | 93 | 45 (38–52) | 75 (81.0) | 9.9 (IQR:8.1–11.7) |
| Dynamic EBV DNA | ORR | 1,000 copies/mL | Shi 2022 (4) | China | Prospective (phase II) |
KL-A167 | recurrent or metastatic | >1 | 132 | 49 (26−68) | 109 (82.6) | 21.7(95%CI: 19.8−22.5) |
| Dynamic EBV DNA | ORR | NR | Chiang 2022 (28) | Hong Kong,China | Prospective (phase II) |
Bintrafusp alfa | recurrent or metastatic | >1 | 38 | NR | NR | 14.9 (1.6-23.3) |
| Dynamic EBV DNA | PFS | NR | Yang 2021 (3) | China | Prospective (phase III) |
Camrelizumab combined with chemo (GP) |
recurrent or metastatic | 1 | 134 | 52 (40–58) | 113 (84.0) | 10.2 (IQR:7.7–12.7) |
| Dynamic EBV DNA | PFS | NR | Chen 2022 (27) | China | Prospective (phase II) |
Toripalimab combined with chemoradiotherapy | metastatic | ≥1 | 22 | 54.5 (IQR: 40.5-57.5) | 15(68.2) | NR |
| PD-L1 | ORR | 1%,10% | Yang 2021 (14) | China | Prospective (phase II) |
Camrelizumab | recurrent or metastatic | >2 | 156 | 48 (23–71) | 124 (79.5) | 14.2 (0.7–27.6) |
| PD-L1 | ORR | 1%,10% | Ma 2018 (2) | Hong Kong, China | Prospective (phase II) |
Nivolumab | recurrent or metastatic | >1 | 45 | 57(37-76) | 35 (77.8) | 12.5 (2.2-22.0) |
| PD-L1 | ORR, PFS | 1%, 25% | Wang 2021 (9) | China | Prospective (phase II) |
Toripalimab | recurrent or metastatic | >2 | 190 | 46(22-71) | 158 (83.2) | NR |
| PD-L1 | ORR, PFS | 1%,10% | Park 2020 (12) | America | Retrospective | anti-PD-1 antibody therapy | recurrent or metastatic | ≥1 | 42 | 50 (15–74) | 31 (73.8) | 13.7 (2.1–55.3) |
| PD-L1 | ORR | 1% | Shi 2022 (4) | China | Prospective (phase II) |
KL-A167 | recurrent or metastatic | >1 | 132 | 49 (26−68) | 109 (82.6) | 21.7(95%CI: 19.8−22.5) |
| PD-L1 | PFS | 1% | Hua 2021 (21) | China | Prospective (phase II) |
Toripalimab combined with radiocherapy | recurrence | 1 | 25 | 49(IQR: 43.5–52.5) | 18 (72.0) | 14.6 (IQR: 13.1–16.2) |
| PD-L1 | PFS | 1%, 5% | Mai 2021 (24) | China | Prospective (phase III) |
Toripalimab combined with chemo(GP) |
recurrent or metastatic | 1 | 130 | 46(19–72) | 124 (85.0) | 17.9 |
| TMB | ORR, PFS | 2.1muts/Mb | Park 2020 (12) | America | Retrospective | anti-PD-1 antibody therapy | recurrent or metastatic | ≥1 | 42 | 50 (15–74) | 31 (73.8) | 13.7 (2.1–55.3) |
| TMB | ORR, PFS | 4muts/Mb | Xu L 2022 (26) | China | Prospective (phase I/II) |
Camrelizumab or Nivolumab | recurrent or metastatic | ≥1 | 57 | 47(25-72) | 43(75.4) | 5.8 |
| TMB | PFS | 2.9muts/Mb | Wang 2021 (9) | China | Prospective (phase II) |
Toripalimab | recurrent or metastatic | >2 | 190 | 46(22-71) | 158 (83.2) | NR |
| TMB | PFS | NR | Hua 2021 (21) | China | Prospective (phase II) |
Toripalimab combined with radiocherapy | recurrence | 1 | 25 | 49(IQR: 43.5–52.5) | 18 (72.0) | 14.6 (IQR: 13.1–16.2) |
| TMB | PFS | NR | Fang 2018 (23) | China | Prospective (phase I) |
Cohort1: Camrelizumab monotherapy |
recurrent or metastatic | >1 | 93 | 45 (38–52) | 75 (81.0) | 9.9 (IQR:8.1–11.7) |
| TMB | PFS | NR | Ma 2021 (25) | China | Prospective (phase I) |
Camrelizumab or Nivolumab | recurrent or metastatic | >1 | 60 | 46 (23–73) | 95 (76.6) | 24.7 (95%CI:23.3- 26.6) |
EBV, Epstein-Barr virus; PD-L1, programmed cell death-ligand 1; TMB, tumor mutation burden; ORR, objective response rate; PFS, progression-free survival; GP, gemcitabine and cisplatin; NR, not reported; IQR, interquartile range; CI, confidence interval.