Immunotherapy for esophageal cancer: Where are we now and where can we go

Table 1 Recent phase III studies for immune checkpoint inhibitor therapy in patients with advanced/metastatic esophageal squamous cell carcinoma

Trail	Line	Phase	n	Country	Intervention	Programmed cell death 1 ligand 1 status	Primary endpoints	Treatment-related adverse events
RATIONALE-302[8]	Later	III	512	Global	Tislelizumab vs CT	Overall	OS (improved in treatment arm)	Fewer in treatment arm
RATIONALE-306[9]	First	III	649	Global	Tislelizumab + CT vs placebo + CT	Overall	OS (improved in treatment arm)	Similar between groups
JUPITER-06[10]	First	III	514	China	Toripalimab + CT vs placebo + CT	Overall	PFS, OS (improved in treatment arm)	Simiral between groups
ORIENT-15[11]	First	III	659	Global (mainly China)	Sintilimab + CT vs placebo + CT	Overall, CPS ≥ 10	PFS, OS (improved in treatment arm)	Simiral between groups
ASTRUM-007[12]	First	III	551	China	Serplulimab + CT vs placebo + CT	CPS ≥ 1	PFS, OS (improved in treatment arm)	Simiral between groups
ESCORT-1st[13]	First	III	596	China	Camrelizumab + CT vs CT	Overall	PFS, OS (improved in treatment arm)	Simiral between groups
ESCORT[14]	Later	III	457	China	Camrelizumab vs CT	Overall	OS (improved in treatment arm)	Similar between groups

CT: Chemotherapy; PFS: Progression-free survival; OS: Overall survival; CPS: Combined positive score.

Table 2 Recent phase II studies for perioperative immune checkpoint inhibitor therapy in patients with esophageal squamous cell carcinoma, n (%)

Trail	Line	Phase	n	Country	Intervention	Population	Primary endpoints	TRAE ≥ Grade 3
Zhang et al[15]	NA	II	47	China	Sintilimab + CT	cStage II-IVA	PCR (22.2)	40.4
Yang et al[16]	NA	II	47	China	Camrelizumab + CT	cStage II-III	PCR (33.3) and MPR (64.3)	8.5
NICE[17]	NA	II	60	China	Camrelizumab + CT	cT1b-4aN2-3M0-1	PCR (39.2)	56.7
ESONICT-1[18]	NA	II	30	China	Sintilimab + CT	cT3-4aN0-3M0	PCR (21.7) and TRAE	3.3
KEEP-G 03[19]	NA	II	30	China	Sintilimab + CT	cT1b-3NanyM0 or cT4aN0-1M0	Safety and Surgical feasibility	36.7
TD-NICE[20]	NA	II	45	China	Tislelizumab + CT	cT2-4aNanyM0	PCR (40.0) and MPR (57.5)	42.2

CT: Chemotherapy; PCR: Pathological complete response; MPR: Major pathological response; TRAE: Treatment-related adverse events.