Initial systemic therapy for metastatic esophageal squamous cell carcinoma

The selection of initial systemic therapy for advanced unresectable and metastatic esophageal squamous cell carcinoma is presented here. Our general approach is to select a backbone chemotherapy regimen and then decide whether to pair it with immunotherapy, based on tumor biomarker status. Listed treatments are preferred options, although alternative agents that are not listed may also be effective. Patients who are ineligible for or unable to tolerate the suggested regimens should be offered other better-tolerated therapies or evaluated for best supportive care. Clinical trials are encouraged if available. For further details on evidence, refer to UpToDate content on systemic therapy for advanced and metastatic esophageal and gastric cancer.

CAPOX: capecitabine and oxaliplatin; CPS: combined positive score; dMMR: mismatch repair deficiency; FOLFIRI: fluorouracil, leucovorin, irinotecan; FOLFOX: fluorouracil, leucovorin, oxaliplatin; modified FLOT: fluorouracil, leucovorin, oxaliplatin, and docetaxel; MSI-H: microsatellite instability high; MSS: microsatellite stable; PD-L1: programmed cell death ligand 1; pMMR: mismatch repair proficiency.

* FOLFIRI is an acceptable alternative for those unable to receive oxaliplatin (eg, due to peripheral neuropathy). FOLFIRI is administered alone without additional agents.

¶ Options include infusional fluorouracil plus leucovorin, capecitabine, oral S-1 (where available), irinotecan, paclitaxel, docetaxel, or dose-reduced CAPOX. Patients who are unable to tolerate these regimens should be evaluated for best supportive care.

Δ There is risk of early-disease progression and death with nivolumab plus ipilimumab. Patients treated with this regimen should be closely monitored for treatment response and switched to alternative agents in the event of disease progression.

◊ For patients with CPS <1, we do not typically incorporate immunotherapy given that the overall survival benefits are limited in this population.

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Initial systemic therapy for metastatic esophageal squamous cell carcinoma