A review of the current evidence for maintenance therapy in gastric cancer.

[OBJECTIVES] Gastric cancer (GC) is usually diagnosed at an advanced stage, and although partial or complete remission can be achieved after first- or second-line treatment, minimal residual disease may remain, with the potential risk of repopulation and recurrence. The main goals of maintenance therapy (MT) at this stage are to prolong progression-free survival (PFS) and overall survival (OS), attenuate adverse events (AEs), and maintain quality of life (QoL). In recent years, there has been a gradual increase in studies on maintenance therapy in advanced and metastatic GC. In this article, we systematically review the studies on MT in GC to assess the current knowledge on the mechanism of action, clinical applications, and biomarkers of this treatment approach.

[METHODS] We searched Embase, Web of Science, PubMed, and Cochrane Library databases, including the period from the inception of the databases through 6 June 2025. Searches were conducted using search terms related to GC and MT. The primary outcomes were PFS and OS, while secondary outcomes included AEs and QoL.

[RESULTS] The core mechanism of MT is to inhibit the proliferation and recurrence of tumor cells through continuous low-intensity treatment. Specific mechanisms include inhibiting angiogenesis and tumor cell proliferation, regulating the tumor microenvironment (TME), enhancing the body's immune surveillance and clearance of tumors, and regulating tumor dormancy. In clinical practice, sustained low-dose application of single chemotherapeutic agents, targeted agents, immune checkpoint inhibitors, and combinations as the mainstay of MT can be clinically important in the maintenance phase of GC patients by inhibiting tumor growth, proliferation, and recurrence to prolong the PFS and OS, while improving QoL. Among them, capecitabine, S-1, bevacizumab, and avelumab were most frequently evaluated. Biomarkers are crucial for predicting treatment response and efficacy in GC MT, monitoring treatment effectiveness, assessing prognosis, and optimizing drug development. Hemoglobin levels, programmed cell death ligand 1 combined positive score, immune (biomarker-positive) or angiogenesis-dominant (biomarker-negative) status, TME characteristics, and C-X-C motif chemokine ligand 12 have shown potential use as indicators for assessing the efficacy of GC MT.

[CONCLUSION] MT, whether applied as a continuous or switching strategy, may sustain clinical benefits without compromising QoL due to severe AEs. Future studies should investigate the long-term clinical benefits of MT and its impact on resource utilization and health-related QoL.