Abstract Background Immune checkpoint inhibitors (ICI) have revolutionized care in oncology with improved overall survival in several cancer populations. Nivolumab has recently been approved for use in patients with upper gastrointestinal cancers. We quantitatively summarized the efficacy and safety of Nivolumab use in patients with advanced esophageal, gastroesophageal, and gastric carcinoma compared to standard chemotherapy. Methods Systemic search of electronic databases was performed to analyze phase III randomized controlled trials (RCTs) comparing Nivolumab versus standard chemotherapy in patients with advanced upper gastrointestinal cancers. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Data were pooled using random effects model via RevMan 5.4 software. Results Four RCTs with a total of 3369 patients and a median follow-up of 13 months were included. The patients’ mean age was 61 ± 20 years, 74.6% were males, and 26% had ≥1% PD-L1 expression. Compared to the chemotherapy group, Nivolumab group had a significantly favorable OS and PFS [HR 0.81;95% CI (0.74, 0.89), p < .001], [HR 0.82;95% CI (0.69, 0.98), p = .03], respectively. Nivolumab significant effect was only in patients with ≥1% PD L1 expression [HR 0.72; 95% CI (0.58, 0.89), p < .001]. No statistical difference was detected between groups regarding serious adverse effects (AE) [OR 1.47; 95%CI (0.94,2.31), p = 0.09]. Conclusions Compared to standard chemotherapy, the use of Nivolumab in patients with advanced esophageal, gastroesophageal, and gastric cancers is associated with improved overall and progression-free survival, with similar rates of AE and AE leading to death. The improvement in survival was significant in patients with ≥1% PD L1 expression.

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Efficacy and safety of Nivolumab in patients with advanced esophageal, gastroesophageal, and gastric cancers: a meta-analysis of randomized controlled trials

What is known and objective An increasing number of targeted drugs have been used to treat advanced or metastatic gastric cancer (GC) and gastroesophageal junction cancer (GEJC). However, the optimal treatment efficacy of these drugs is still controversial. The aims of this study are to systematically summarize the efficacy and safety of current targeted drugs for advanced or metastatic GC and GEJC. Methods PubMed, EmBase, Cochrane Library, Web of Science and ClinicalTrials were searched for double-blind randomized controlled trials (RCTs) on GC and GEJC up to December 2019. Additionally, we updated the literature search from Jan, 1, 2020 to September 30, 2021. Narrative and quantitative analysis were performed to analyse the efficacy and safety. STATA 15.1 was used to identify publication bias, and the SUCRA (surface under the cumulative ranking) curve was conducted to rank the treatments for each outcome. Results A total of 27 RCTs with 9295 GC and GEJC patients treated by 19 drugs were included. SUCRA showed that regorafenib was the most likely to improve patients' progression-free survival (96.4%), followed by apatinib (90.7%), nivolumab (82.4%), everolimus (76.5%) and pertuzumab (68.5%). Meanwhile, apatinib (92.4%) was most likely to improve overall survival, followed by nivolumab (87.9%), regorafenib (72.5%), olaparib (67.7%) and lapatinib (63.2%). Additionally, neutropenia, diarrhoea and fatigue were the most common adverse events caused by these drugs, followed by pain, nausea, decreased appetite, anaemia and vomiting. What is new and conclusion Regorafenib and nivolumab have higher efficacy and tolerability and are the most advantageous for advanced GC and GEJC. Moreover, apatinib has higher efficacy but lower tolerability. Everolimus and pertuzumab combined with chemotherapy have best secondary higher efficacy for progression-free survival and good tolerability. Lapatinib and olaparib combined with chemotherapy have moderate efficacy for overall survival and good tolerability.

Long Ge

Papers

Efficacy and safety of targeted drugs in advanced or metastatic gastric and gastroesophageal junction cancer: A network meta-analysis.