Maintenance Therapy in Metastatic Gastric Cancer: A Multicenter Retrospective Study in Colombia

Background: Gastric cancer is the fifth most frequent cancer and the third cause of cancer-related death worldwide, with high incidence in Asia and Latin America. In Colombia, most cases are diagnosed at advanced stages. Platinum and fluoropyrimidine combinations remain the standard first-line treatment for metastatic disease, but the optimal duration of first-line chemotherapy and the role of maintenance strategies are not clearly established. The randomized phase II AIO MATEO trial showed that S-1 maintenance after induction chemotherapy achieved overall survival comparable to continued chemotherapy with less toxicity. Immunotherapy and targeted therapies (such as trastuzumab in HER2-positive disease) are also used in the maintenance setting in selected molecular subgroups. No Colombian data exist on the outcomes of these maintenance strategies.

Design: Observational, retrospective, multicenter cohort study based on review of medical records at four high-complexity cancer centers in Bogotá, Colombia: Hospital Universitario Fundación Santa Fe de Bogotá (coordinating center, through the Instituto de Cáncer Carlos Ardila Lülle), Centro de Tratamiento e Investigación sobre Cáncer Luis Carlos Sarmiento Angulo (CTIC), Clínica del Country and Los Cobos Medical Center.

Population: Adults (older than 18 years) with metastatic gastric cancer diagnosed and treated between 2013 and 2023 who achieved at least stable disease by RECIST after induction chemotherapy, with ECOG performance status of 2 or less, and who subsequently received maintenance therapy. All eligible patients will be included (census sampling); no sample size calculation is required.

Data collection: Data will be abstracted from institutional medical records into a single REDCap database hosted by Fundación Santa Fe de Bogotá. Each center will have restricted user accounts limited to its own patients. Records will be coded with an alphanumeric identifier, and the identification key will remain locally at each center and will not be uploaded. Variables include demographic and clinical characteristics, comorbidities, Helicobacter pylori status, histology (WHO and Lauren classifications, differentiation), molecular markers (microsatellite instability, PD-L1, HER2), AJCC 8th edition staging, induction and maintenance regimens and number of cycles, immunotherapy and targeted therapy, adverse drug reactions, laboratory values and tumor markers, dates of progression and relapse, vital status and cause of death.

Statistical analysis: Qualitative variables will be summarized with absolute and relative frequencies and quantitative variables with means and standard deviations or medians and interquartile ranges according to their distribution. Overall and progression-free survival will be estimated with the Kaplan-Meier method and reported as medians and survival rates. Exploratory comparisons of outcomes among maintenance types (fluoropyrimidines, immunotherapy, targeted therapy) will use bivariate tests and adjusted multivariable models, considering the molecular profile as a potential effect modifier. Analyses will be performed with IBM SPSS Statistics 25.

Ethics: The study is classified as research without risk under Colombian Resolution 8430 of 1993, and individual informed consent is not required for this retrospective record review. The protocol was approved by the Comité Corporativo de Ética en Investigación of Fundación Santa Fe de Bogotá (CCEI-18065-2025) and by the ethics committees of the participating institutions. Data will be handled in accordance with the Declaration of Helsinki and Colombian Law 1581 of 2012 on personal data protection, stored securely for five years and then destroyed.

• Fluoropyrimidine Maintenance Therapy (Drug), also known as Capecitabine, 5-Fluorouracil, S-1: Fluoropyrimidine-based maintenance therapy (capecitabine, 5-fluorouracil or S-1) administered after induction chemotherapy in routine clinical practice. The study does not assign or modify treatment; exposure data are abstracted retrospectively from medical records.
• Immune Checkpoint Inhibitor Maintenance (Drug), also known as Nivolumab, Pembrolizumab, Atezolizumab: Immune checkpoint inhibitors (such as nivolumab, pembrolizumab or atezolizumab) administered as part of maintenance therapy in routine clinical practice. The study does not assign or modify treatment.
• Targeted Therapy Maintenance (Drug), also known as Trastuzumab: Targeted therapy (such as trastuzumab in HER2-positive disease) administered as part of maintenance therapy in routine clinical practice. The study does not assign or modify treatment.

Primary outcomes

• Overall Survival [From start of maintenance therapy until death from any cause or last follow-up, assessed up to 10 years]

Secondary outcomes

• Progression-Free Survival [From start of maintenance therapy until disease progression, death or last follow-up, assessed up to 10 years]
• Best Response to Maintenance Therapy [From start of maintenance therapy until disease progression or end of maintenance, assessed up to 10 years]
• Survival Rate at 6 Months and 1, 2, 3, 4 and 5 Years [6 months and 1, 2, 3, 4 and 5 years after diagnosis]
• Number of Patients With Adverse Drug Reactions During Maintenance Therapy [From start of maintenance therapy until end of maintenance, assessed up to 10 years]
• Cancer-Specific Mortality [From diagnosis until death or last follow-up, assessed up to 10 years]

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Patients older than 18 years diagnosed with metastatic gastric cancer at a participating institution between 2013 and 2023 who received fluoropyrimidines, immunotherapy or targeted therapy as maintenance therapy.
* At least stable disease according to RECIST criteria after initial induction treatment, with ECOG performance status of 2 or less, followed by maintenance therapy with fluoropyrimidines.
* Medical record showing institutional oncology follow-up.

Exclusion Criteria:

* Biopsies that do not meet the quality and adequacy criteria required for analysis.
* No clinical or imaging follow-up at the institution after diagnosis and treatment.
* Metastatic gastric cancer treated exclusively with palliative care without fluoropyrimidine maintenance chemotherapy.
* Discontinuation of fluoropyrimidine maintenance therapy before the first follow-up assessment because of toxicity or medical decision, without evaluation of treatment response.
* Death during the diagnostic process before tumor classification and staging were completed.

• Stocker G, Lorenzen S, Ettrich T, Herz AL, Longo F, Kiani A, Venerito M, Trojan J, Mahlberg R, Moosmann N, Chibaudel B, Kubicka S, Greil R, Daum S, Geissler M, Larcher-Senn J, Keller G, Lordick F, Haag GM. S-1 maintenance therapy in Caucasian patients with metastatic esophagogastric adenocarcinoma-final results of the randomized AIO MATEO phase II trial. ESMO Open. 2023 Jun;8(3):101572. doi: 10.1016/j.esmoop.2023.101572. Epub 2023 Jun 2. PMID 37270871

• Henry Alexander Vargas, MD, Principal investigator, Fundación Santa Fe de Bogotá