Page 70 - Helicobacter pylori and Gastric Cancer: From Tumor microenvironment to Immunotherapy

Clinical trial studies of PD-1 blockade approach in gastric cancer
It is evident within cancers evolutionary pressure exists to avoid attack by the immune system. To this end cancer cells can employ signals the body uses to control self-damaging autoimmunity. Especially PD-1 appears prominent in limiting immunity towards cancers cells. In physiology, PD1 guards against autoimmunity through a dual mechanism of promoting programmed cell death in cytotoxic T-cells while simultaneously reducing apoptosis in regulatory T cells. By engaging PD1 on anti-tumor immune cells through its cognate ligands, in particular, PD-L1 the cancer cell can corrupt anti-oncogenic immunity. Anti PD1 antibodies prevent this interaction by binding to the relevant immune cells. Accordingly, anti-PD-1 antibodies have shown such anticancer efficacy in various cancers types[6]. Concerning this strategy, its safety and effectiveness were tested with pembrolizumab is patients from the Asian-Pacific patients who presented with progressive gastric or gastroesophageal junction tumors and exhibited a positive PD- L1 expression status. Concerning the latter, the eligibility criteria were that patients should have or ≥ 1% cancer nest cell PD-L1 staining. The design involved a gift of 10 mg of pembrolizumab per kg once in two weeks for one year or until comprehensive response, advancement or unacceptable toxicity. The primary efficacy endpoint was evaluated after eight weeks medical imaging, whereas duration of response constituted a secondary endpoint. In this study, the overall response was 22% (95% CI, 10.39) and 33% (95% CI, 19.50) respectively, which although an encouraging result not markedly better as compared to studies employing unselected patients. Hence, the PD-L1 expression per se is suitable for selecting gastric cancer patients for PD-1-directed checkpoint therapy remains poor and other approaches need to be explored.
In a clinical trial NCT02267343[19], involving the use of Nivolumab on gastro- oesophageal junction or advanced gastric cancer refractory patient, the cohort with intolerant of, at least two preceding treatment regimens were recruited in a placebo- controlled, double-blinded randomized clinical trial involving 493 patients who were assigned randomly to take nivolumab. 8.87 months (IQR 6.57-12.37) was the follow-up median for surviving patients in the nivolumab group. 5.26 months with (95% CI 4.60-6.37) is the overall survival median in the nivolumab group. The overall survival rate of 26.2% was observed within the nivolumab group compare to 10.9% within the placebo group. There is grade 4 treatment-related adverse effect in 10% of the 330 patients from the Nivolumab arm of the study[19].
Chapter 3
Chapter 3
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