# Relative Clinical Efficacy and Safety of Second- or Later-Line Treatments for Advanced and Metastatic Gastric Cancer: A Rapid Review and Network Meta-Analysis

## TL;DR

This study compares the effectiveness and safety of various later-line treatments for advanced gastric cancer, finding no major differences in key outcomes.

## Contribution

A network meta-analysis of second- or later-line gastric cancer treatments reveals no significant efficacy or safety advantages over established therapies.

## Key findings

- No statistically significant differences in overall survival, progression-free survival, or objective-response rate across treatments.
- Pembrolizumab showed a decreased risk of severe adverse effects compared to paclitaxel.
- Novel treatments have not significantly improved efficacy or safety outcomes compared to established options.

## Abstract

To identify randomised control trials (RCTs) of treatments (recommended by the National Comprehensive Cancer Network (NCCN), the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines and clinical expertise) for the second- or later-line treatment of advanced/metastatic gastric cancer. To determine the relative efficacy and safety of the treatments.

RCTs were identified from a Rapid Literature Review and a published systematic review. Identified RCTs were subject to data-extraction and narrative review. Eligible RCTs were included in evidence networks to determine relative efficacy and safety of the treatments.

In total, 44 RCTs (pertaining to eleven treatments), were identified for data-extraction and narrative review; 37 in the second-line setting, five in the second- and later-line setting and two in the third- and later-line setting. Evidence networks were feasible for the second-line treatments only. No statistically significant differences, across treatments, for key efficacy outcomes (overall-survival, progression-free survival), and additional outcome (objective-response rate) were identified. Pembrolizumab was associated with a statistically significant decreased risk of Grade ≥ 3 treatment-related adverse effects versus paclitaxel; no other significant differences, across treatments, were identified for this outcome.

The appreciable number of RCTs identified indicates that the treatment landscape here is rapidly evolving. The introduction of novel treatments, in the second-line setting, has not had a statistically significant impact on key efficacy outcomes, and has had little impact on safety outcomes, versus more established treatments. There remains a need for novel treatments that will have a significant benefit on efficacy and safety outcomes.

The online version contains supplementary material available at 10.1007/s12029-026-01407-z.