Page 66 - Helicobacter pylori and Gastric Cancer: From Tumor microenvironment to Immunotherapy

Chapter 3
Chapter 3
advance gastric cancer. Hence we decided to continue with the further analysis of the available public data.
Study characteristics; Expression, Clinical Associations, and Prognosis.
Published articles including six studies on clinical trials including and 18 ongoing clinical trials with 3291 patients at the point of reference, with a most extreme example size of 451 and a base specimen size of 96 members. Most of the investigations accounted for are in Asia (Japan) and the United States, by the geographical variations in gastric cancer incidence. The first clinically tested immune checkpoint is CTLA-4, and two monoclonal antibodies (ipilimumab and tremelimumab) targeting this checkpoint have been developed for clinical use. Based on the experience in other cancers, relatively more attention is now given to the PD-1/PD-L1 checkpoint system that can be targeted by various biologicals including nivolumab, pembrolizumab for PD-1 and atezolizumab, avelumab, durvalumab for PD-L1 respectively. Although not supported by published evidence, it has already been tried to employ such medication for precision medicine, patient selected for experimental immuno-checkpoint inhibition based on high PD-L1 expression (immunohistochemistry for PD-L1 behaves relatively well, hence the choice this marker appears mainly pragmatical). For instance, a phase I trial was conducted involving a cohort of 39 patients selected for PD-L1 immunochemical positivity as assayed employing the 22C3 antibody. Patients were treated after every two weeks with 10 mg/kg of pembrolizumab. There was a 22% overall response rate, but 53.1 % experienced some decrease in tumor size, which is a good result for advanced gastric cancer. Remarkably, an impressively long median response of 40 weeks (range 20–48+) was observed resulting in 11.4 months of the overall survival rate[4]. As stated, these results are remarkable as the patient group involved is refractory to other treatments. A question that needs to be urgently addressed in this respect is the usefulness of triaging patients for PD-L1 expression[5]. The potential of targeting PD-1 in gastric cancer has recently been substantially bolstered by a phase III trial using nivolumab. This trial, which involved heavily pre-treated patients showed 26 percent twelve months survival in the Nivolumab group versus only eleven percent in the placebo group. The results of all published trails involving immune-checkpoint inhibition are provided in Table 1.These antibodies include: BMS-936559, atezolizumab (MPDL3280A),durvalumab (MEDI4736),and avelumab (MSB0010718C, which has proven efficacy in gastrointestinal malignancies[16-18]). Concerning the latter out of 346 eligible patients enrolled,
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