Evaluating comparative effectiveness of pembrolizumab-based therapy versus chemotherapy in treatment of gastric carcinoma: a systematic review and meta-analysis of randomized controlled trials.

Abstract

Gastric cancer, especially cancer of the gastro-esophageal junction, ranks among the first five cancers in the world with the highest mortality rates. It has poor survival rates for the advanced stages. Traditional chemotherapy, while standard, often results in significant side effects and limited efficacy. The objective of this meta-analysis and systemic review is to ascertain if pembrolizumab-based therapies for advanced gastric cancer are more effective and safer than standard chemotherapy. The focus consisted of RCTs with adults suffering from gastric carcinoma who received pembrolizumab every 3 weeks (200 mg) intra-related dose or with at least comparable chemotherapy regimen. Outcomes assessed are as follows: overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). All potential sources regarding the search of outcome measures were applied: Google Scholar, Scopus, PubMed, and Cochrane library, and last search in June 2024 was carried out. Out of 568 articles screened, four RCTs comprising 2,831 patients met the inclusion criteria. Analysis indicated that pembrolizumab alone did not significantly improve OS compared to chemotherapy (HR 0.87). However, when combined with chemotherapy, pembrolizumab dramatically enhanced OS (HR 0.80) and PFS (HR 0.78). ORR was superior in the pembrolizumab plus chemotherapy group (RR 1.24), while pembrolizumab monotherapy showed no significant difference from chemotherapy alone. Safety analysis revealed a higher frequency of adverse events in the pembrolizumab-based therapy groups compared to chemotherapy. Pembrolizumab together with chemotherapy improves greater survival and higher levels of response rate in patients with severe gastric cancer, especially with high PD-L1 expression. But it has rather more adverse events, allowing patient monitoring with care.