Table 1.
The baseline characteristics of the RCTs included in this meta-analysis (Total of 69 clinical trials).
| NO | First author and year | Study | Treatment lines | Tumor type | Drug | PD-1/ PD-L1 | Treatment regimen | Enrollment |
|---|---|---|---|---|---|---|---|---|
| PD-1/PD-L1 + chemotherapy VS chemotherapy | ||||||||
| 1 | Forde PM, 2022 (15) | CheckMate 816 (NCT 02998528) | first line | NSCLC | Nivolumab | PD-1 | Nivolumab + platinum-based chemotherapy VS platinum-based chemotherapy | 352 |
| 2 | Langer CJ, 2016 (16) | KEYNOTE-021 (NCT 02039674) | first line | NSCLC | Pembrolizumab | PD-1 | Pembrolizumab + carboplatin VS carboplatin + pemetrexed | 121 |
| 3 | Rodríguez-Abreu D, 2021 (17) | KEYNOTE-189 (NCT 02578680) | first line | NSCLC | Pembrolizumab | PD-1 | Pembrolizumab + pemetrexed-platinum VS pemetrexed-platinum | 607 |
| Garassino MC, 2023 (18) | ||||||||
| 4 | Novello S, 2023 (19) | KEYNOTE-407 (NCT 02775435) | first line | NSCLC | Pembrolizumab | PD-1 | Pembrolizumab + carboplatin+paclitaxel/nab-paclitaxel VS carboplatin + paclitaxel/nab-paclitaxel | 558 |
| 5 | Zhou C, 2021 (20) | CameL (NCT 03134872) | first line | NSCLC | Camrelizumab | PD-1 | Camrelizumab + carboplatin + pemetrexed VS carboplatin + pemetrexed | 412 |
| 6 | Wang Z, 2023 (21) | CHOICE-01 (NCT 03856411) | first line | NSCLC | Toripalimab | PD-1 | Toripalimab + nab-paclitaxel + carboplatin VS nab-paclitaxel + carboplatin | 464 |
| 7 | Lu Z, 2022 (22) | ORIENT-15(NCT 03748134) | first line | ESCC | Sintilimab | PD-1 | Sintilimab + cisplatin + paclitaxel VS cisplatin + paclitaxel | 659 |
| 8 | Luo H, 2021 (23) | ESCORT-1st (NCT 03691090) | first line | ESCC | Camrelizumab | PD-1 | Camrelizumab + paclitaxel + cisplatin VS paclitaxel + cisplatin | 595 |
| 9 | Wang ZX, 2022 (24) | JUPITER-06 (NCT 03829969) | first line | ESCC | Toripalimab | PD-1 | Toripalimab + paclitaxel + cisplatin VS paclitaxel + cisplatin | 514 |
| 10 | Xu J, 2023 (25) | RATIONALE-306 (NCT 03783442) | first line | ESCC | Tislelizumab | PD-1 | Tislelizumab + platinum agent and fluoropyrimidine/capecitabine/paclitaxel VS platinum agent and fluoropyrimidine/capecitabine/paclitaxel | 645 |
| 11 | Janjigian YY, 2021 (26) | CheckMate 649 (NCT 02872116) | first line | GJC | Nivolumab | PD-1 | Nivolumab + capecitabine+oxaliplatin / leucovorin+fluorouracil+oxaliplatin VS capecitabine+oxaliplatin / leucovorin+fluorouracil+oxaliplatin | 1549 |
| 12 | Kang YK, 2022 (27) | CheckMate 649 (NCT 02872116) | first line | GC/GJC | Nivolumab | PD-1 | Nivolumb + oxaliplatin + capecitabine VS oxaliplatin + capecitabin | 717 |
| 13 | Tolaney SM, 2020 (28) | NCT 03051659 | second or others | BRCA | Pembrolizumab | PD-1 | Pembrolizumab + eribulin VS eribulin | 88 |
| 14 | Schmid P, 2022 (29) | KEYNOTE-522 (NCT 03036488) | first line | TNBC | Pembrolizumab | PD-1 | Pembrolizumab + paclitaxel + carboplatin VS paclitaxel + carboplatin | 1172 |
| 15 | Powles T, 2021 (30) | KEYNOTE-361 (NCT 02853305) | first line | UC | Pembrolizumab | PD-1 | Pembrolizumab + gemcitabine+cisplatin/carboplatin VS gemcitabine+cisplatin/carboplatin | 691 |
| 16 | Mai HQ, 2021 (31) | JUPITER-02 (NCT 03581786) | first line | NPC | Toripalimab | PD-1 | Toripalimab +gemcitabine-cisplatin VS gemcitabine-cisplatin | 289 |
| 17 | Yang Y, 2021 (32) | CAPTAIN-1st(NCT 03707509) | first line | NPC | Camrelizumab | PD-1 | Camrelizumab + gemcitabine + cisplatin VS gemcitabine + cisplatin | 263 |
| 18 | Nishio M, 2021 (33) | IMpower132 (NCT 02657434) | first line | NSCLC | Atezolizumab | PD-L1 | Atezolizumab + carboplatin / cisplatin and pemetrexed VS carboplatin / cisplatin and pemetrexed | 565 |
| 19 | Socinski MA, 2018 (34) | IMpower150 (NCT 02366143) | first line | NSCLC | Atezolizumab | PD-L1 | Atezolizumab + bevacizumab + carboplatin + paclitaxel VS bevacizumab + carboplatin + paclitaxel | 787 |
| Reck M, 2020 (35) | ||||||||
| 20 | West H, 2019 (36) | IMpower130 (NCT 02367781) | first line | NSCLC | Atezolizumab | PD-L1 | Atezolizumab + carboplatin + nab-paclitaxel VS carboplatin + nab-paclitaxel | 705 |
| 21 | Zhou C, 2022 (37) | GEMSTONE-302 (NCT 03789604) | first line | NSCLC | Sugemalimab | PD-L1 | Sugemalimab + platinum-based chemotherapy VS platinum-based chemotherapy | 479 |
| 22 | Johnson ML, 2023 (38) | POSEIDON (NCT 03164616) | first line | NSCLC | Durvalumab | PD-L1 | Durvalumab + platinum-based chemotherapy VS platinum-based chemotherapy | 667 |
| 23 | Paz-Ares L, 2019 (39) | CASPIAN(NCT 03043872) | first line | SCLC | Durvalumab | PD-L1 | Durvalumab + platinum–etoposide VS platinum–etoposide | 531 |
| Goldman JW, 2021 (40) | ||||||||
| 24 | Wang J, 2022 (41) | CAPSTONE-1(NCT 03711305) | first line | SCLC | Adebrelimab | PD-L1 | Adebrelimab + carboplatin + etoposide VS carboplatin + etoposide | 462 |
| 25 | Pusztai L, 2021 (42) | I-SPY2 (NCT 01042379) | first line | BRCA | Durvalumab | PD-L1 | Durvalumab + olaparib + paclitaxel VS paclitaxel | 372 |
| 26 | Emens LA, 2021 (43) | IMpassion130 (NCT 02425891) | first line | TNBC | Atezolizumab | PD-L1 | Atezolizumab + nab-paclitaxel VS nab-paclitaxel | 890 |
| 27 | Mittendorf EA, 2020 (44) | IMpassion031 (NCT 03197935) | first line | TNBC | Atezolizumab | PD-L1 | Atezolizumab + nab-paclitaxel + doxorubicin + cyclophosphamide VS nab-paclitaxel + doxorubicin + cyclophosphamide | 331 |
| 28 | Pujade-Lauraine E, 2021 (45) | JAVELIN Ovarian 200(NCT 02580058) | first line | Multiple cancers | Avelumab | PD-L1 | Avelumab + pegylated liposomal doxorubicin VS pegylated liposomal doxorubicin | 359 |
| 29 | Lee NY, 2021 (46) | JAVELIN Head and Neck 100(NCT 02952586) | first line | HNSCC | Avelumab | PD-L1 | Avelumab+chemoradiotherapy VS chemoradiotherapy | 692 |
| 30 | Monk BJ, 2021 (47) | JAVELIN Ovarian 100(NCT 02718417) | first line | EOC | Avelumab | PD-L1 | Avelumab + carboplatin + paclitaxel VS carboplatin + paclitaxel + observation | 662 |
| 31 | Moore KN, 2021 (48) | IMagyn050/GOG 3015/ENGOT-OV39(NCT 03038100) | first line | OC | Atezolizumab | PD-L1 | Atezolizumab + bevacizumab + carboplatin + paclitaxel VS bevacizumab + carboplatin + paclitaxel | 1286 |
| 32 | Powles T, 2022 (49) | IMbassador 250 (NCT 03016312) | second or others | PCA | Atezolizumab | PD-L1 | Atezolizumab + enzalutamide VS enzalutamide | 750 |
| 33 | Mettu NB, 2022 (50) | BACCI (NCT 02873195) | second or others | CRC | Atezolizumab | PD-L1 | Atezolizumab + capecitabine + bevacizumab VS capecitabine + bevacizumab | 132 |
| 34 | Galsky MD, 2020 (51) | IMvigor130 (NCT 02807636) | first line | UC | Atezolizumab | PD-L1 | Atezolizumab+platinum-based chemotherapy VS platinum-based chemotherapy | 843 |
| PD-1/PD-L1 VS chemotherapy | ||||||||
| 1 | Huang J, 2020 (52) | ESCORT (NCT 03099382) | second or others | ESCC | Camrelizumab | PD-1 | Camrelizumab VS docetaxel/irinotecan | 448 |
| 2 | Kojima T, 2020 (53) | KEYNOTE-181 (NCT 02564263) | second or others | ESCC | Pembrolizumab | PD-1 | Pembrolizumab VS paclitaxel/docetaxel/irinotecan | 610 |
| 3 | Chan ATC, 2023 (54) | KEYNOTE-122 (NCT 02611960) | second or others | NPC | Pembrolizumab | PD-1 | Pembrolizumab VS capecitabine/gemcitabine/docetaxel | 228 |
| 4 | Diaz LA Jr, 2022 (55) | KEYNOTE-177 (NCT 02563002) | first line | CRC | Pembrolizumab | PD-1 | Pembrolizumab VS 5-fluorouracil–based therapy | 296 |
| André T, 2020 (56) | ||||||||
| 5 | Powles T, 2021 (30) | KEYNOTE-361 (NCT 02853305) | first line | UC | Pembrolizumab | PD-1 | Pembrolizumab VS gemcitabine+cisplatin/carboplatin | 644 |
| 6 | Winer EP, 2021 (57) | KEYNOTE-119 (NCT 02555657) | second or others | TNBC | Pembrolizumab | PD-1 | Pembrolizumab VS capecitabine/eribulin/gemcitabine/vinorelbine | 601 |
| 7 | Herbst RS, 2016 (58) | KEYNOTE-010 (NCT 01905657) | second or others | NSCLC | Pembrolizumab | PD-1 | Pembrolizumab VS docetaxel | 652 |
| 8 | Mok TSK, 2019 (59) | KEYNOTE-042 (NCT 02220894) | first line | NSCLC | Pembrolizumab | PD-1 | Pembrolizumab VS platinum-based chemotherapy | 1251 |
| de Castro G Jr, 2023 (60) | ||||||||
| 9 | Borghaei H, 2015 (61) | CheckMate 057 (NCT 01673867) | second or others | NSCLC | Nivolumab | PD-1 | Nivolumab VS docetaxel | 555 |
| 10 | Sezer A, 2021 (62) | EMPOWER-Lung 1 (NCT 03088540) | first line | NSCLC | Cemiplimab | PD-1 | Cemiplimab VS platinum-doublet chemotherapy | 697 |
| 11 | Barlesi F, 2018 (63) | JAVELIN Lung 200 (NCT 02395172) | second or others | NSCLC | Avelumab | PD-L1 | Avelumab VS docetaxel | 758 |
| 12 | Jassem J, 2021 (64) | IMpower110 (NCT 02409342) | first line | NSCLC | Atezolizumab | PD-L1 | Atezolizumab VS platinum-based chemotherapy | 549 |
| Herbst RS, 2020 (65) | ||||||||
| 13 | Galsky MD, 2020 (51) | IMvigor130 (NCT 02807636) | first line | UC | Atezolizumab | PD-L1 | Atezolizumab VS platinum-based chemotherapy | 744 |
| 14 | van der Heijden MS, 2021 (66) | IMvigor211 (NCT 02302807) | second or others | UC | Atezolizumab | PD-L1 | Atezolizumab VS vinflunine/paclitaxel/docetaxel | 902 |
| 15 | Powles T, 2020 (67) | DANUBE (NCT 02516241) | first line | UC | Durvalumab | PD-L1 | Durvalumab VS gemcitabine+cisplatin/carboplatin | 658 |
| 16 | Pujade-Lauraine E, 2021 (45) | JAVELIN Ovarian 200(NCT 02580058) | first line | Multiple cancers | Avelumab | PD-L1 | Avelumab VS pegylated liposomal doxorubicin | 364 |
| PD-1/PD-L1 VS placebo | ||||||||
| 1 | Choueiri TK, 2021 (68) | KEYNOTE-564 (NCT 03142334) | second or others | RCC | Pembrolizumab | PD-1 | Pembrolizumab VS placebo | 984 |
| Powles T, 2022 (69) | ||||||||
| 2 | Janjigian YY, 2021 (70) | KEYNOTE-811 (NCT 03615326) | second or others | GC | Pembrolizumab | PD-1 | Pembrolizumab VS Placebo | 433 |
| 3 | Cohen EEW, 2019 (71) | KEYNOTE-040 (NCT 02252042) | second or others | HNSCC | Pembrolizumab | PD-1 | Pembrolizumab VS Standard-of-Care | 480 |
| 4 | Colombo N, 2021 (72) | KEYNOTE-826 (NCT 03635567) | first line | CCA | Pembrolizumab | PD-1 | Pembrolizumab VS Placebo | 616 |
| 5 | Eggermont AMM, 2020 (73) | KEYNOTE-054(NCT 02362594) | second or others | melanoma | Pembrolizumab | PD-1 | Pembrolizumab VS Placebo | 1011 |
| 6 | Long GV, 2022 (74) | KEYNOTE-716 (NCT 03553836) | second or others | melanoma | Pembrolizumab | PD-1 | Pembrolizumab VS Placebo | 969 |
| 7 | Zimmer L, 2020 (75) | IMMUNED (NCT 02523313) | second or others | melanoma | Nivolumab | PD-1 | Nivolumab VS Placebo | 107 |
| 8 | Fennell DA, 2021 (76) | CONFIRM (NCT 03063450) | second or others | mesothelioma | Nivolumab | PD-1 | Nivolumab VS placebo | 332 |
| 9 | Sugawara S, 2021 (77) | TASUKI-52 (NCT 03117049) | first line | NSCLC | Nivolumab | PD-1 | Nivolumab VS Placebo | 548 |
| 10 | Antonia SJ, 2017 (78) | PACIFIC (NCT 02125461) | second or others | NSCLC | Durvalumab | PD-L1 | Durvalumab VS Placebo | 709 |
| 11 | Zhou Q, 2022 (79) | GEMSTONE-301 (NCT 03728556) | second or others | NSCLC | Sugemalimab | PD-L1 | Sugemalimab VS placebo | 381 |
| 12 | Felip E, 2021 (80) | IMpower010 (NCT 02486718) | second or others | NSCLC | Atezolizumab | PD-L1 | Atezolizumab VS placebo | 990 |
| Kenmotsu H, 2022 (81) | ||||||||
| 13 | Horn L, 2018 (82) | IMpower133 (NCT 02763579) | first line | SCLC | Atezolizumab | PD-L1 | Atezolizumab VS Placebo | 394 |
| 14 | Bellmunt J, 2021 (83) | IMvigor010 (NCT 02450331) | first line | UC | Atezolizumab | PD-L1 | Atezolizumab VS Observation | 787 |
| 15 | Pal SK, 2022 (84) | IMmotion010(NCT 03024996) | second or others | RCC | Atezolizumab | PD-L1 | Atezolizumab VS placebo | 773 |
| PD-1/PD-L1 + CTLA-4 VS PD-1/PD-L1 | ||||||||
| 1 | Antonia SJ, 2016 (85) | CheckMate 032 (NCT 01928394) | second or others | SCLC | Nivolumab | PD-1 | Nivolumab + ipilimumab VS nivolumab | 159 |
| 2 | Boyer M, 2021 (86) | KEYNOTE-598 (NCT 03302234) | first line | NSCLC | Pembrolizumab | PD-1 | Pembrolizumab+ipilimumab VS pembrolizumab | 563 |
| 3 | Gettinger SN, 2021 (87) | Lung-MAP S1400I(NCT 02785952) | second or others | SCLC | Nivolumab | PD-1 | Nivolumab + ipilimumab VS nivolumab | 247 |
| 4 | Hodi FS, 2018 (88) | CheckMate 067 (NCT 01844505) | first line | melanoma | Nivolumab | PD-1 | Nivolumab + ipilimumab VS Nivolumab | 626 |
| 5 | Powles T, 2020 (67) | DANUBE (NCT 02516241) | first line | UC | Durvalumab | PD-L1 | Durvalumab + tremelimumab VS Durvalumab | 685 |
| PD-1/PD-L1 + CTLA-4 VS chemotherapy | ||||||||
| 1 | Baas P, 2021 (89) | CheckMate 743 (NCT 02899299) | first line | pleural mesothelioma | Nivolumab | PD-1 | Nivolumab + ipilimumab VS chemotherapy | 584 |
| 2 | Paz-Ares L, 2021 (90) | CheckMate 9LA (NCT 03215706) | first line | NSCLC | Nivolumab | PD-1 | Nivolumab + ipilimumab VS chemotherapy | 707 |
| 3 | Powles T, 2020 (67) | DANUBE (NCT 02516241) | first line | UC | Durvalumab | PD-L1 | Durvalumab + tremelimumab VS Chemotherapy | 653 |
PD-1, Programmed cell death 1; PD-L1, Programmed cell death 1 ligand 1; CTLA-4, anti-cytotoxic T-lymphocyte antigen-4; HR, Hazard Ratios; OR, Odds Ratio; CI, Confidence Interval; RE, Random Effect; FE, Fixed Effect; NSCLC, Non-Small-Cell Lung Cancer; SCLC, Small-Cell Lung Cancer; BRCA, Breast Cancer; UC, Urothelial Carcinoma; HNSCC, Head and Neck Squamous Cell Carcinoma; CCA, Cervical Cancer; TNBC, Triple-Negative Breast Cancer; GC, Gastric Cancer; GC/GJC, Gastric or gastro-oesophageal junction cancer; ESCC, Oesophagea/Esophagea Squamous Cell Carcinoma; NPC, Nasopharyngeal Cancer; CRC, Colorectal Cancer; EOC, Epithelial Ovarian Cancer; OC, Ovarian Cancer; GEC, Gastroesophageal adenocarcinoma; RCC, Renal Cell Carcinoma; PCA, Prostate Cancer; HCC, Hepatocellular Carcinoma; EC, Esophageal Cancer; MPM, Malignant Pleural Mesothelioma.