Systematic literature review and meta-analysis of clinical outcomes for previously treated patients with advanced gastric or gastroesophageal junction cancer.

Abstract

e16054 Background: Standard of care treatment in advanced (unresectable and/or metastatic) gastric or gastroesophageal junction (GEJ) cancer includes chemotherapies with or without targeted therapies. While there have been many studies undertaken in this patient population, there exists uncertainty around the efficacy of these treatments. A systematic literature review and meta-analysis were conducted to assess clinical outcomes of chemotherapies with or without targeted therapies. Methods: A systematic literature review was conducted through mid-2021 to identify relevant studies using Embase, MEDLINE, and Cochrane Central Register of Controlled trials (January 1, 2000–July 6, 2021) with additional searches of recent annual ASCO and ESMO conferences. Eligible studies included randomized controlled trials (RCTs), controlled clinical trials, and non-randomized clinical trials of any pharmacologic treatments licensed by the FDA or EMA among patients (≥18 years age, Eastern Cooperative Oncology Group performance score 0 or 1) previously treated for advanced gastric or GEJ cancer and who had progressed on prior treatment (i.e., ≥2L). A meta-analysis of objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were conducted among RCTs of relevant therapies for ≥2L gastric cancers. The ORR meta-analysis was performed using the Freeman-Tukey double arcsine transformation. For time-to-event outcomes, published Kaplan-Meier curves for OS and PFS were digitized to create pseudo- individual patient data. A meta-analysis of the resulting pooled survival curves for OS and PFS were conducted following the methodology of Combescure et al. (2014). Results: Of the 214 studies identified, 42 RCTs (77 trial arms) evaluating relevant therapies including 7,256 participants were included in the meta-analysis of ORR. The random effects pooled estimate of ORR was 15.0% (95% confidence interval [CI]: 12.7-17.5%). Median PFS (32 studies; 61 survival curves) was 3.5 months (95% CI: 3.2-3.7) with PFS rates at 6, 12, and 24 months of 25.8% (95% CI: 23.1-28.8%), 7.3% (95% CI: 6.0-8.9%), and 0.7% (95% CI: 0.4-1.0%), respectively. Median OS (34 studies; 64 survival curves) was 7.9 months (95% CI: 7.4-8.5) with OS rates at 6, 12, and 24 months of 62.5% (95% CI: 59.0-66.2%), 30.4% (95% CI: 27.7-33.3%), and 6.7% (95% CI: 5.4-8.4%), respectively. Conclusions: The standard treatments have demonstrated limited efficacy in previously treated patients with advanced gastric or GEJ cancers. Newer treatments (e.g., immunotherapies) to address this unmet medical need should be thoroughly investigated and evaluated.