Initial approach to systemic treatment of esophagogastric cancer

HER2: human epidermal growth factor receptor 2; PD-L1: programmed cell death ligand-1; dMMR: deficient mismatch repair; MSI-H: microsatellite instability-high; pMMR: proficient mismatch repair; CPS: combined positive score; FU: fluorouracil; FOLFOX: oxaliplatin, leucovorin plus bolus and short-term infusional FU; CAPOX/XELOX: capecitabine plus oxaliplatin; TPS: Tumor Proportion Score.

* Refer to text for guidelines for exclusion of patients for trastuzumab on the basis of excess cardiac risk.

¶ Refer to text for discussion of options for backbone cytotoxic regimen to combine with trastuzumab.

Δ While the chemotherapy backbone in the KEYNOTE-590 trial was cisplatin plus FU many clinicians prefer an oxaliplatin-containing regimen (eg, FOLFOX, CAPOX [XELOX]) in this setting.

◊ Patients with squamous cell carcinoma and low levels of PD-L1 expression can be treated with immunotherapy plus chemotherapy. However, we have a lower threshold to omit or discontinue immunotherapy for unfavorable baseline features (eg, CPS <1, significant non-cancerous lung disease, experiencing toxicity) than PD-L1 high disease. We do not favor immunotherapy alone due to concerns about early disease progression/death compared with chemotherapy alone.

§ For patients with HER2-negative esophagogastric adenocarcinoma, mismatch repair proficient disease, and CPS <5, data suggest limited benefit for adding immunotherapy to chemotherapy. However, opinions differ on the use of immunotherapy in this population. Refer to UpToDate content on systemic therapy for esophageal and gastric cancer.