First-line maintenance strategies and later-line options in patients with advanced gastroesophageal adenocarcinoma

The treatment landscape for patients with advanced gastric or gastroesophageal junction adenocarcinoma is evolving, driven by a deeper understanding of molecular profiling and the introduction of novel anticancer drugs. Systemic chemotherapy has improved survival compared to supportive care; however, overall survival worldwide remained limited to approximately 1 year. Recently, the introduction of upfront immune checkpoint inhibitors (ICIs) and/or targeted agents in biomarker-enriched populations has led to clinically meaningful survival improvements. The expansion of treatment options for metastatic disease, combined with the identification of biomarker-selected populations, underscores the importance of tailoring first-line, maintenance, and sequential therapies across multiple lines. In this context, the delivery of an effective first-line treatment is crucial, as less than half of patients retain fitness for additional anti-cancer therapies due to the morbidity associated with disease progression to the initial regimen even within modern clinical trials regardless of the use of targeted therapy or immunotherapy combined with chemotherapy. On the other hand, the expanding therapeutic armamentarium including ICIs, antibody-drug conjugates, and targeted therapies for molecularly selected subgroups, will enable the development of sequential treatment strategies across multiple lines of therapy. This review summarizes the current knowledge about maintenance strategies and subsequent lines of treatment in either biomarker selected and unselected populations.