Systemic treatments for resectable carcinoma of the esophagus

Table 1 The immunotherapies for resectable esophageal cancer patients

Name	Ref.	Number of patients	Treatment regimens	Outcome	Conclusion
Camrelizumab	Wu et al[48], 2021	12	Cisplatin + paclitaxel + camrelizumab = 8; carboplatin + paclitaxel + camrelizumab = 4	MPR, 5/7 (71.43%)	Patients with ESCC had an MPR rate of 42.11%; The SLD regression rate has a certain guiding relevance for the impact of immunotherapy, and the adoption of the NACI regimen may not raise the likelihood of problems in neoadjuvant treatment and surgery
Camrelizumab	Liu et al[49], 2022	60	Carboplatin + paclitaxel + camrelizumab	Proceeded to surgery, 51/60 (85.00%); R0 resection, 50/51 (98.00%); pCR, 5/20 (39.20%)	Camrelizumab plus weekly chemotherapy as a promising neoadjuvant treatment for locally advanced ESCC, and further phase 3 randomized controlled trial is warranted
Camrelizumab	Liu et al[50], 2022	56	Cisplatin + paclitaxel + camrelizumab	Proceeded to surgery, 51/56 (77.40%); pCR, 18/56 (39.20%); MPR, 12/56 (21.43%)	Camrelizumab plus neoadjuvant chemotherapy in resectable ESCC demonstrates promising efficacy with acceptable toxicity, providing a feasible and effective option
Pembrolizumab	Li et al[51], 2021	20	Carboplatin + paclitaxel + pembrolizumab + radiotherapy	Proceeded to surgery, 18/20 (90.00%); pCR, 10/18 (55.60%)	PPCT was safe and did not delay surgery in resectable EC
Pembrolizumab	Zhu et al[53], 2022	31	Carboplatin + paclitaxel + pembrolizumab + radiotherapy	Proceeded to surgery, 28/29 (96.55%); pCR, 7/31 (22.58%)	Incorporating anti–PD-1 therapy into neoadjuvant chemoradiation and adjuvant treatment of GEJ adenocarcinoma may improve pCR and survival
Pembrolizumab	Huang et al[54], 2021	54	Nedaplatin + docetaxel + pembrolizumab = 23 vs. nedaplatin + docetaxel = 31	pCR 30.4%/9.7%; ORR 86.9%/95.7%	Pembrolizumab combined with chemotherapy showed promising activity with a manageable safety profile and it could offer a potential new neoadjuvant treatment approach for patients with ESCC
Pembrolizumab	Duan et al[55], 2022	18	Nedaplatin + paclitaxel + pembrolizumab = 13 or nedaplatin + docetaxel +	Proceeded to surgery, 13/18 (72.22%); MPR, 9/13 (69.20%); pCR, 6/13 (46.15%)	The combination of neoadjuvant immunotherapy and chemotherapy for ESCC is associated with a high pathological response and immunologic effects in the tumor microenvironment
			pembrolizumab = 5
Tislelizumab	Yan et al[56], 2022	45	Carboplatin + paclitaxel + tislelizumab	Proceeded to surgery, 36/45 (80.00%); MPR (69.20%); pCR (50.00%)	Tislelizumab plus chemotherapy as neoadjuvant therapy demonstrates promising antitumor activity for resectable ESCC with high rates of MPR, pCR, and R0 resection, as well as acceptable tolerability
Sintilimab	Chen et al[57], 2023	30	Cisplatin + S1 + paclitaxel + sintilimab	Proceeded to surgery, 30/30 (100.00%); MPR (50.00%); pCR (20.00%)	Neoadjuvant sintilimab plus platinum-based triplet chemotherapy appeared safe and feasible, did not delay surgery and induced a pCR rate of 20.0% in patients with potentially resectable ESCC
Atezolizumab	van den Ende et al[58], 2021	40	Carboplatin + Paclitaxel + Atezolizumab + Radiotherapy	Proceeded to surgery, 33/40 (82.50%); MPR (50.00%); pCR, 10/40 (25.00%)	The addition of atezolizumab to conventional nCRT for resectable EC was feasible without compromising surgical outcomes
Toripalimab	Xing et al[59], 2021	30	Cisplatin + paclitaxel + toripalimab D3 vs. cisplatin + paclitaxel + toripalimab D1	Proceeded to surgery, 11/15 vs. 13/15; pCR 4/15 vs. 1/15	The study showed that delaying toripalimab to day 3 in chemoimmunotherapy might achieve a higher pCR rate than that on the same day
Toripalimab	He et al[60], 2022	20	Carboplatin + paclitaxel + toripalimab	Proceeded to surgery, 16/20; R0 resection, 14/16; MPR, 7/16; pCR, 4/16	The combination of toripalimab plus paclitaxel and carboplatin is safe, feasible, and effective in locally advanced resectable ESCC
Toripalimab	Gao et al[61], 2022	20	Cisplatin + docetaxel + toripalimab	ORR, 14/20; MPR, 5/12; pCR, 2/12	Toripalimab combined with docetaxel and cisplatin as a novel neoadjuvant therapy was safe and effective in locally advanced ESCC
Toripalimab	Zhang et al[62], 2023	60	S1 + paclitaxel + toripalimab	R0 resection, 55/60; MPR, 27/60; pCR, 16/60	Neoadjuvant therapy with toripalimab, nab-paclitaxel and S1 was less toxic and showed promising antitumor activity in patients with resectable ESCC
Nivolumab	Kelly et al[63], 2021	794	Chemoradiotherapy+ nivolumab = 532 vs. chemoradiotherapy+ placebo = 262	DFS, 22.4/11.0 mo; distant recurrence, 29/39%; locoregional recurrence, 12/17%	Nivolumab adjuvant treatment significantly increased DFS compared to placebo in patients with resected esophagus or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy

DFS: Disease-free survival; EC: Esophageal cancer; ESCC: Esophageal squamous cell carcinoma; GEJ: Gastroesophageal junction; MPR: Major pathological response; NACI: Neoadjuvant chemotherapy combined with immunotherapy; nCRT: Neoadjuvant chemoradiotherapy; ORR: Objective response rate; pCR: Pathological complete response; PD-1: Programmed cell death protein 1; SLD: Sum of lesion diameter; PPCT: Preoperative pembrolizumab with concurrent chemoradiotherapy.