A systematic review and meta-analysis to evaluate the efficacy and safety of nivolumab for advanced esophageal, gastroesophageal, and gastric cancer.

Abstract

e16060 Background: Esophageal, gastroesophageal, and gastric cancers make up about 1% of the cancer cases in the United States and most patients are diagnosed at advanced stages. Despite treatment options available, these patients have a median survival of about one year. Due to the advancement in treatment using immune checkpoint inhibitors in cancer therapy, this class of medications were recently approved for their use in patients with esophageal, gastroesophageal, and gastric cancer. A literature review and meta-analysis was conducted to evaluate the efficacy and safety of use of nivolumab in these group of patients. Methods: We systematically searched multiple databases using pre-specified search terms. We included only RCTs comparing Nivolumab with/without chemotherapy versus chemotherapy, in patients with advanced esophageal, gastroesophageal, or gastric cancer. Co-primary outcomes were overall survival (OS) and progression free survival (PFS). We also reported response rates, sensitivity analysis and adverse effects (AE), using fixed effects model via RevMan 5.4 software. Results: Three RCTs were included with a total of 2,645 patient and a median follow-up of 13 months. The patients’ mean age was 62±22 years, 75% were males, 79% were stage IV metastatic disease, and 29% had ≥1% PD-L1 expression. Compared to the chemotherapy group, Nivolumab group had a significantly favorable OS and PFS [HR 0.78;95% CI (0.69, 0.87), P < 0.001], [HR 0.83;95% CI (0.75, 0.92), P < 0.001] respectively. Sensitivity analysis showed significant effect of Nivolumab only in patients with ≥1 % PD L1 expression [HR 0.71; 95% CI (0.64, 0.80), P < 0.001]. Chemotherapy group had a significantly favorable outcome regarding serious AE [OR 1.57;95% CI (1.28, 1.93), P < 0.001], and diarrhea [OR 1.29;95% CI (1.07, 1.56), P = 0.007], with no difference regarding AE leading to death [OR 1.75;95% CI (0.88, 3.47), P = 0.11]. Conclusions: The use of nivolumab in patients with advanced esophageal, gastroesophageal, and gastric cancers is associated with improved disease-free survival and overall survival compared to treatment with chemotherapy, albeit at an increased risk of serious adverse effects. The improvement in survival was significant in patients with ≥1% PD L1 expression.