Clin Oncol | Volume 7, Issue 1 | Research Article | Open Access

Systematic Review and Meta-Analysis of PD-1 and CTLA-4 Bispecific Antibody in the Treatment of Gastric Cancer

Zakari Shaibu1,2, Wei Zhu2*, Zhi-Hong Chen3*, Dinah Donna Twum-Ampofo4, Lynna Bayorbor5 and Kelvin Asamoa-Agyapong6

1Overseas Education College, Jiangsu University, China
2School of Medicine, Jiangsu University, China
3Department of Gastrointestinal Surgery, Affiliated People’s Hospital of Jiangsu University, China
4Medfocus International, 3 Sam Nujoma Road North Ridge, Accra, Ghana
5Gomoa Potsin Polyclinic Accra, Ghana
6Korle Bu Teaching Hospital, Accra, Ghana

*Correspondance to: Zhi-Hong Chen 

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Background: When treating esophageal or Gastric/Gastroesophageal Junction (G/GEJ) cancer, the PD-1/CTLA-4 dual blockade consistently showed a greater response rate compared to PD-1 monotherapy but increased toxicity.
Objective: The aim of this study is to evaluate the effectiveness and safety of PD-1/CTLA-4 therapy in patients with esophageal or G/GEJ cancer.
Method: An update of a Cochrane systematic review, and network meta-analysis comparing randomized trials evaluating Pembrolizumab, Ipilimumab and Nivolumab was performed. A database search from PubMed, Google Scholar, Medline, and Web of Science and Cochrane Library for randomized and non-randomized control trials involving treatment with PD-1 and CTLA-4
published from May 3rd, 2016 to March 23rd, 2022 was retrieved from original data. A total of 15 studies investigating outcomes such as Overall Survival (OS), Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), Objective Response Rate (ORR), Progression Free Survival (PFS), Disease Control Rate (DCR), Duration of Response (DOR) and Treatment Related Adverse Effect (TRAE) were analyzed. For PD-1 versus control, meta-analyses were performed using Rev-Man 5.3 on six studies.
Result: The final 15 studies with total number of 2,971 patients were included. Out of the 15 studies, 6 was included in the meta-analysis. The combination therapy of CTLA-4 and PD-1 resulted in improved OS (59%), CR (4%), PR (22%), SD (26%), ORR (36%), and PFS (47%). Results of the meta-analysis between PD-1 and control confirmed that the control group which is made up
different chemotherapy regimens was more beneficial than PD-1 monotherapy in terms of OS (Heterogeneity: Tau2=0.10; Chi2=9.23, df=4 (P=0.06); I2=57%), PFS (Heterogeneity: Chi2=16.13, df=3 (P=0.001); I2=81%) and DCR (Heterogeneity: Tau2=0.03; Chi2=22.00, df=1 (P<0.00001); I2=95) The incidence of grade 3/4 TRAE increased with the combination therapy but there was no significant difference between chemotherapy and PD-1 monotherapy.
Conclusion: Combination therapy of CTLA-4 and PD-1 in this current study was superior to CTLA-4 or PD-1 monotherapy in terms of OS, CR, PR, SD, ORR and PFS, but the side effects of combination therapy were higher than monotherapy. Also, PD-1 monotherapy is not as effective when used compared to chemotherapy regimens. Considering the response variations to this
combination therapy usage, more individualized treatments should be introduced in clinical practice.


Gastric cancer; Gastro-esophageal junction cancer; PD-1/CTLA-4 inhibitors; Immunotherapy; Checkpoint inhibitors


Shaibu Z, Zhu W, Chen Z-H, Twum-Ampofo DD, Bayorbor L, Asamoa-Agyapong K. Systematic Review and Meta-Analysis of PD-1 and CTLA-4 Bispecific Antibody in the Treatment of Gastric Cancer. Clin Oncol. 2022;7:1950..

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