Clinical Outcomes for Previously Treated Patients with Advanced Gastric or Gastroesophageal Junction Cancer: A Systematic Literature Review and Meta-Analysis

Purpose Although second-line treatments improve survival compared to best supportive care in patients with advanced gastric cancer with disease progression on first-line therapy, prognosis remains poor. A systematic review and meta-analysis were conducted to quantify the efficacy of second-or-later line systemic therapies in this target population. Methods A systematic literature review (January 1, 2000 to July 6, 2021) of Embase, MEDLINE, and CENTRAL with additional searches of 2019–2021 annual ASCO and ESMO conferences was conducted to identify studies in the target population. A random-effects meta-analysis was performed among studies involving chemotherapies and targeted therapies relevant in treatment guidelines and HTA activities. Outcomes of interest were objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) presented as Kaplan–Meier data. Randomized controlled trials reporting any of the outcomes of interest were included. For OS and PFS, individual patient-level data were reconstructed from published Kaplan–Meier curves. Results Forty-four trials were eligible for the analysis. Pooled ORR (42 trials; 77 treatment arms; 7256 participants) was 15.0% (95% confidence interval (CI) 12.7–17.5%). Median OS from the pooled analysis (34 trials; 64 treatment arms; 60,350 person-months) was 7.9 months (95% CI 7.4–8.5). Median PFS from the pooled analysis (32 trials; 61 treatment arms; 28,860 person-months) was 3.5 months (95% CI 3.2–3.7). Conclusion Our study confirms poor prognosis among patients with advanced gastric cancer, following disease progression on first-line therapy. Despite the approved, recommended, and experimental systemic treatments available, there is still an unmet need for novel interventions for this indication.