The Anti-PD-1/PD-L1 Immunotherapy for Gastric Esophageal Cancer: A Systematic Review and Meta-Analysis and Literature Review

Abstract

Background: Treatment options for advanced gastric esophageal cancer are quite limited. Chemotherapy is unavoidable at certain stages, and research on targeted therapies has mostly failed. The advent of immunotherapy has brought hope for the treatment of advanced gastric esophageal cancer. The aim of the study was to analyze the safety of anti-PD-1/PD-L1 immunotherapy and the long-term survival of patients who were diagnosed as gastric esophageal cancer and received anti-PD-1/PD-L1 immunotherapy. Method: Studies on anti-PD-1/PD-L1 immunotherapy of advanced gastric esophageal cancer published before February 1, 2020 were searched online. The survival (e.g. 6-month overall survival, 12-month overall survival (OS), progression-free survival (PFS), objective response rates (ORR)) and adverse effects of immunotherapy were compared to that of control therapy (physician’s choice of therapy). Results: After screening 185 studies, 4 comparative cohort studies which reported the long-term survival of patients receiving immunotherapy were included. Compared to control group, the 12-month survival (OR = 1.67, 95% CI: 1.31 to 2.12, P < 0.0001) and 18-month survival (OR = 1.98, 95% CI: 1.39 to 2.81, P = 0.0001) were significantly longer in immunotherapy group. The 3-month survival rate (OR = 1.05, 95% CI: 0.36 to 3.06, P = 0.92) and 18-month survival rate (OR = 1.44, 95% CI: 0.98 to 2.12, P = 0.07) were not significantly different between immunotherapy group and control group. The ORR were not significantly different between immunotherapy group and control group (OR = 1.54, 95% CI: 0.65 to 3.66, P = 0.01). Meta-analysis pointed out that in the PD-L1 CPS ≥10 sub group population, the immunotherapy could obviously benefit the patients in tumor response rates (OR = 3.80, 95% CI: 1.89 to 7.61, P = 0.0002). Conclusion: For the treatment of advanced gastric esophageal cancer, the therapeutic efficacy of anti-PD-1/PD-L1 immunotherapy was superior to that of chemotherapy or palliative care.

Comparative Impact of PD-1 and PD-L1 Inhibitors on Advanced Esophageal or Gastric/Gastroesophageal Junction Cancer Treatment: A Systematic Review and Meta-Analysis

“…As the most direct measure of clinical benefit, outcomes of the OS post-treatment with PD-1/PD-L1 inhibitors in trials with esophageal or G/GEJ cancer patients were incongruous. Although previous metaanalyses consistently exhibited improvements in the OS rather than the PFS in esophageal or G/GEJ cancer treatment with PD-1/PD-L1 inhibitor, limitations such as the lack of controlled data or the possibility of known/unknown biases increasing heterogeneity in the analysis might result in less statistically powerful conclusions [6,9]. Furthermore, a previous study included only two studies in the analysis demonstrating improvement of the OS and PFS in the control group, rather than the anti-PD-1 or anti-PD-L1 groups, to treat esophageal or G/GEJ cancer patients [36].…”

“…Pathophysiologically, gastrointestinal tumors are traditionally considered nonimmune-related malignancies. However, current reports have provided a new direction in the treatment by demonstrating the effectiveness of blocking specific immunosuppressive substances, such as programmed death receiver 1/programmed death ligand 1 (PD-1/PD-L1) [6]. Current studies have indicated that the number of tumor-infiltrating lymphocytes is related to tumor prognosis [7] and the correlation between malignant tumors and immune cells such as T cells.…”

A Network Pharmacological Elucidation of the Systematic Treatment Activities and Mechanisms of the Herbal Drug FDY003 Against Esophageal Cancer

“…79 The programmed death-ligand 1 (PD-L1)/programmed death-1 (PD-1) checkpoint pathway may be important for the prediction of disease-free survival, overall survival, cancer relapse, treatment response rate and susceptibility, metastasis, lymph node invasion, tumor stage, and incidence of post-therapeutic adverse effects in patients with EC. 80–82 The modulation of this pathway can inhibit immunosuppression, tumorigenicity, self-renewal, immune escape, proliferation, metastasis, EMT, and treatment resistance of EC cells and tumors, and can enhance the antitumor immune response and survival in EC. 80–82 The TNF pathway determines the treatment sensitivity, viability, and growth of EC cells and tumors.…”

Esophagogastric junction adenocarcinoma: Preoperative chemoradiation or perioperative chemotherapy?

“…Recent studies have demonstrated survival advantages with monoclonal antibodies targeting PD-1/PD-L1 ( e.g. , pembrolizumab, nivolumab) in patients with advanced gastric esophageal cancer[ 26 ].…”