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

Abstract

Programmed death 1 (PD-1) and PD ligand 1 (PD-L1) inhibitors have demonstrated varying effectiveness in treating esophageal or gastric/gastroesophageal junction (G/GEJ) cancer. Hence, this systematic review and meta-analysis evaluated the efficacy and safety of anti-PD-1/PD-L1 treatment in patients with esophageal or G/GEJ cancer by analyzing the types of medications. Randomized controlled trials comparing anti-PD-1/PD-L1 to control therapy were identified by searching PubMed, EMBASE, and ClinicalTrials.gov. The outcomes included overall survival (OS), progression-free survival (PFS) rates, and serious adverse events (SAEs), evaluating the differences in therapy types, including a comparison between PD-1 and PD-L1 inhibitors. Eight studies were included in the analysis. PD-1/PD-L1 inhibitors affected the overall OS rate increment without influencing the PFS rate (HR, 0.837; 95% CI, 0.753–0.929; p = 0.001; HR 0.991; 95% CI, 0.778–1.263; p = 0.942, respectively). Anti-PD-1 was significantly more beneficial for increasing OS and PFS than PD-L1 inhibitors. Anti-PD-1 and PD-L1 use was not significantly associated with SAE development in esophageal or G/GEJ cancer patients. PD-1/PD-L1 inhibitor use was associated with improved OS and PFS rate increase among PD-1 and PD-L1 inhibitors. Considering response variations to anti-PD-1/PD-L1 usage, more individualized treatments should be introduced in clinical practice.

Efficacy of PD-1/PD-L1 inhibitors in patients with advanced gastroesophageal cancer: An updated meta-analysis based on randomized controlled trials

“…This present systematic review and meta-analysis was performed to investigate the clinical efficacy of PD-1/PD-L1 inhibitors on advanced gastroesophageal cancer as well as the relationship between clinicopathological features and the curative effects of PD-1/PD-L1 inhibitors. Consistent with the results of previous meta-analyses ( Chen et al, 2021 ; Formica et al, 2021 ; Oh et al, 2021 ), we found that PD-1/PD-L1 inhibitors (monotherapy or combined with chemotherapy) were associated with a prolongation of OS in patients with esophageal cancer, gastroesophageal junction cancer and gastric cancer, and it should be emphasized that no significant improvement in PFS was observed. Although both OS and PFS are regarded as important survival outcomes of response efficacy in anticancer treatment, the link between the two has yet to be fully proved.…”

“…Previously, subgroup analyses of markers affecting the efficacy of PD-1/PD-L1 inhibitors in gastroesophageal cancer were performed through two meta-analyses ( Formica et al, 2021 ; Oh et al, 2021 ), but given the limited number of studies included, inconsistency of research design and significant heterogeneity among the included studies, the credibility of their results and conclusions seemed limited. Hence, based on the latest evidence from randomized controlled trials (RCTs), an updated meta-analysis will be executed to probe the clinical efficacy of PD-1/PD-L1 inhibitors in advanced gastroesophageal cancer and the association between patients' clinicopathological features (therapeutic schedules, sex, age, etc.)…”

Influence of Helicobacter pylori infection on PD‐1/PD‐L1 blockade therapy needs more attention

“…In summary, PD‐1/PD‐L1 blockade therapy in gastric cancer should be certified further 50 . In addition, it is imperative to explore whether there are more factors to comprehensively evaluate suitable patients and cancer types for effective PD‐1/PD‐L1 blockade therapy in gastric cancer 51‐53 .…”

“…In summary, PD-1/PD-L1 blockade therapy in gastric cancer should be certified further. 50 In addition, it is imperative to explore whether there are more factors to comprehensively evaluate suitable patients and cancer types for effective PD-1/PD-L1 blockade therapy in gastric cancer. [51][52][53] Only by determining the adaptability of PD-1/PD-L1 blockade therapy can the ICIs for gastric cancer could get a breakthrough.…”

Therapeutic strategies for gastric cancer targeting immune cells: Future directions

“…Tumor cells can escape the killing of tumor cells by T cells through downregulating MHC and upregulating the expression of inhibitory receptors such as PD-L1, CTLA-4, LAG-3, TIM-3 and TIGIT ( 32 – 34 ), and blocking the binding of these inhibitory receptors to ligands can restore T-cell anti-tumor activity ( 35 ). PD-1/PD-L1 monoclonal antibodies (mAbs) demonstrate significant anti-tumor effect and prolong overall survival (OS) in various malignancies ( 36 – 38 ). PD-1 is an immunosuppressive receptor that is highly expressed on TILs ( 35 ), whereas PD-L1 as the main ligand of PD-1 is highly expressed on the surface of tumor cells ( 39 ).…”