Exploring program death-1 and cytotoxic T lymphocyte antigen-4 safety in gastric cancer clinical trials: A meta-analysis

TL;DR

This study finds that PD-1 treatment for advanced gastric cancer causes fewer severe side effects compared to control treatments, though combining PD-1 with CTLA-4 increases adverse events.

Contribution

The study provides a meta-analysis of adverse events in gastric cancer patients treated with PD-1 and CTLA-4 inhibitors, comparing monotherapy and combination therapy.

Findings

PD-1 monotherapy reduces the risk of grade 3-4 adverse events like nausea and fatigue compared to control.

Combining PD-1 with CTLA-4 increases treatment-related adverse events in gastric cancer patients.

PD-1 treatment is associated with a higher occurrence of pruritus compared to control.

Abstract

Gastric cancer is one of the leading causes of cancer-related deaths worldwide. Despite advances in treatment options, the overall prognosis for advanced gastric cancer remains poor. Immunotherapy has revolutionized the field of cancer treatment by harnessing the patient’s immune system to target and destroy cancer cells. Two important immune checkpoint inhibitors that have shown promise in various malignancies, including gastric cancer, are program death-1 and cytotoxic T lymphocyte-4 inhibitors.

To assess and analyze the occurrence of adverse events associated with program death-1 and cytotoxic T lymphocyte antigen-4 in patients diagnosed with advanced gastric cancer.

Relevant studies were searched in reputable databases such as PubMed, Embase, Google Scholar, and the Cochrane Library from October 6, 2017, to February 3, 2022. Studies were analyzed with Review Manager 5.4. PROSPERO: CRD42023479662.

Of the 500 studies retrieved, nine randomized control trials involving 5,185 patients were included in the meta-analysis comparing TRAEs in advanced gastric cancer patients after immune checkpoint inhibitor monotherapy and combined immune checkpoint inhibitors treatment. There was a lower risk of any grade of treatment-related adverse events with program death -1 than in the control arm (76.5% vs. 79%, P = 0.02). Program death-1 observed a lesser risk of grade 3-4 treatment-related adverse events as compared to the control for nausea (0.3% vs. 3%, P = 0.007) and fatigue (1% vs. 2.7%, P = 0.006). Program death-1 monotherapy also saw a decrease in the incidence of common treatment-related adverse events such as diarrhea (9.6% vs. 16%, P < 0.00001), nausea (6.8% vs. 20.6%, P < 0.00001) and fatigue (11% vs. 15.9%, P = 0.001). However, pruritus occurrence increased (3.8% vs. 9%, P < 0.001) after program death-1 compared to control.

Patients with advanced gastric cancer endured program death-1 treatment effectively. Nonetheless, the combination of program death-1 and cytotoxic T lymphocyte-4 results in a greater occurrence of treatment-related adverse events.

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