ABSTRACT
Gastroesophageal cancers are highly diverse tumors in terms of their anatomic and molecular characteristics, making drug development challenging. Recent advancements in understanding the molecular profiles of these cancers have led to the identification of several new biomarkers. Ongoing clinical trials are investigating new targeted agents with promising results. CLDN18.2 has emerged as a biomarker with established activity of associated targeted therapies. Other targeted agents, such as bemarituzumab and DKN-01, are under active investigation. As new agents are incorporated into the treatment continuum, the questions of biomarker overlap, tumor heterogeneity, and toxicity management will need to be addressed.
Subject(s)
Biomarkers, Tumor , Esophageal Neoplasms , Molecular Targeted Therapy , Receptor, ErbB-2 , Stomach Neoplasms , Humans , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/pathology , Molecular Targeted Therapy/methods , Stomach Neoplasms/drug therapy , Stomach Neoplasms/metabolism , Stomach Neoplasms/genetics , Biomarkers, Tumor/metabolism , Receptor, ErbB-2/metabolism , Receptor, ErbB-2/antagonists & inhibitors , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacologyABSTRACT
The optimal approach for treating cytology-positive (Cy1) gastric cancer (GC) patients without additional non-curative factors remains uncertain. While neoadjuvant chemotherapy followed by gastrectomy shows promise, its suitability for Western patients is not well supported by existing data. To address this knowledge gap, a cohort study was conducted across four major GC treatment centers in Lithuania, Estonia, and Ukraine. Forty-three consecutive Cy1 GC patients who underwent neoadjuvant chemotherapy between 2016 and 2020 were enrolled. The study evaluated overall survival (OS), progression-free survival (PFS), cytology status conversion, and major pathological response rates, along with the factors influencing these outcomes. All patients underwent surgery post-neoadjuvant chemotherapy, with 53.5% experiencing cytological status conversion and 23.3% achieving a major pathological response. The median OS and PFS were 20 (95% CI: 16-25) and 19 (95% CI: 11-20) months, respectively. Conversion to negative cytology significantly reduced the relative risk of peritoneal progression (RR: 0.11; 95% CI: 0.03-0.47, p = 0.002). The study suggests that neoadjuvant chemotherapy followed by gastrectomy holds promise as a treatment option for Cy1 GC without additional non-curative factors, associating cytology status conversion with improved long-term outcomes and reduced peritoneal relapse risk.
