# GUIDELINE OBJECTIVES
To provide guidance on the optimal systemic therapies for the treatment of advanced gastric and gastro-esophageal junction (GEJ) carcinoma. Optimal systemic therapies were defined as those that provided improved overall survival and improved quality of life.

# TARGET POPULATION
Adult patients (age 18 years) with advanced gastric carcinoma or advanced carcinoma of the GEJ. In this patient population, advanced disease is defined as non-resectable disease that is either locally advanced, recurrent, or metastatic.

# INTENDED USERS
This guideline is intended for use by clinicians and health care providers involved in the management or referral of the target population.

# Recommendation 1a
Medical oncologists should prescribe either a fluoropyrimidine-oxaliplatin doublet or a fluoropyrimidine-irinotecan doublet regimen in the first-line treatment of patients with locally advanced, recurrent, or metastatic gastric and GEJ carcinoma.

# Qualifying Statements for Recommendation 1a
- Based on improved efficacy with fluoropyrimidine-oxaliplatin-taxane when compared with monotherapy, this triplet regimen may be discussed with selected patients as an alternative to a doublet regimen. - Medical oncologists should individualize treatment based on the different toxicities associated with the preferred regimens, patient characteristics, and patient preferences when choosing the appropriate therapy.

# Recommendation 1b
In patients with metastatic gastric cancer or GEJ carcinoma not overexpressing human epidermal growth factor receptor 2 (HER2), medical oncologists should not prescribe a biological agent in addition to a first-line chemotherapy regimen

# Recommendation 2
In patients with recurrent or metastatic gastric and GEJ carcinoma, medical oncologists should prescribe an immune checkpoint inhibitor (ICI) in addition to a fluoropyrimidine doublet chemotherapy regimen in the first-line setting.

# Qualifying Statements for Recommendation 2
- A positive association was observed between programmed cell death ligand 1 (PD-L1) combined positive score (CPS) and the magnitude of treatment benefit. In Checkmate-649, the overall survival benefit of nivolumab was confined to patients with a CPS of 5. To aid clinicians in informed decision making and counseling, we recommend that the CPS score be obtained, and the recommendation for the use of nivolumab be restricted to those patients whose tumours have a CPS of 5.

# Recommendation 3
In patients with HER2 overexpressing gastric or GEJ carcinoma, medical oncologists should prescribe the addition of trastuzumab to a fluoropyrimidine doublet chemotherapy regimen in the first-line setting.

# Qualifying Statements for Recommendation 3
- Trastuzumab should be prescribed until disease progression or intolerance in HER2 overexpressing patients

# Recommendation 4
In patients with gastric or GEJ adenocarcinoma being considered for second-line therapy, medical oncologists may prescribe paclitaxel plus ramucirumab.

# Qualifying Statements for Recommendation 4
- Single agent irinotecan or taxane is a reasonable alternative for patients not eligible for paclitaxel plus ramucirumab

# Recommendation 5
In patients with gastric or GEJ adenocarcinoma being considered for third-line therapy, medical oncologists may prescribe trifluride-tipiracil monotherapy.

# Recommendation 6
In patients with gastric or GEJ carcinoma undergoing later lines of therapy, medical oncologists should not prescribe ICI in addition to standard of care.

# IMPLEMENTATION CONSIDERATIONS
Although testing for PD-L1 CPS is available in Ontario through local laboratories or the industry funded access programs, CPS is not routinely included on the tumor pathology report. Medical oncologists will need to request CPS testing from available resources. Until reporting of the CPS is routine, requesting the score may result in treatment decision delays.