Effective systemic therapy such as nivolumab as an adjuvant therapy has been demonstrated to improve the outcomes of patients receiving neoadjuvant chemoradiotherapy (CRT) for locoregional esophageal cancer. A more effective systemic therapy with anti-PD-1 or anti-PD-L1 immune checkpoint inhibitors (ICIs) plus cisplatin-based doublet chemotherapy, which has shown with high tumor response rate and improved survivals in patients with late-stage ESCC, may provide crucial benefit to patients with locally advanced disease by improving the systemic control, downstaging the locoregional tumor burden and reducing recurrence and metastasis.
Collectively, the investigators hypothesize that total neoadjuvant therapy (TNT) approach-consisting of induction immunochemotherapy followed by CRT-is a promising strategy to enhance the outcomes for participants with locally advanced esophageal squamous cell carcinoma.
Pathologically proven squamous cell carcinoma of the intrathoracic esophagus.
cT3/4a, N0, M0;
cT1-4a, N1-3, M0.
Tumor length longitudinal ≤ 10cm and radial ≤ 5cm.
Adenocarcinoma
Previous thoracic irradiation
Previous systemic chemotherapy
Has received prior therapy with an anti-PD-1 or anti-PD-L1
Single group
Tislelizumab
Drug200 mg, 1h-IVF, Q3W on day 1 for 2 cycles
Paclitaxel
DrugPaclitaxel 175 mg/m2, 3h-IVF, Q3W on day 1 for 2 cycles
Cisplatin
DrugCisplatin 75 mg/m2, 2h-IVF, Q3W on day 1 for 2 cycles
Chemoradiotherapy
RadiationChemoradiotherapy * Paclitaxel 50 mg/m2, 1h-IVF, on days 1, 8,15, 22, and 29; * Cisplatin 30 mg/m2,1h-IVF, on days 1, 8,15, 22, and 29; * RT: 1.8 Gy/fraction, 5 days a week, for 25 fractions (total dose= 45 Gy).
pathological complete response
To evaluate the pathological complete response (pCR) rate of participants receiving total neoadjuvant therapy with induction immunochemotherapy and chemoradiotherapy (CRT) followed by surgery in operable ESCC.
Major pathological response
defined as number of participants with residual tumor cells ≤10% at the time of surgery divided by the number of participants received esophagectomy
R0 resection rate
defined as number of participants with no gross residual disease, plus negative section margins (i.e., proximal, distal, and circumferential margins are all \> 1 mm) according to pathological examination of esophagectomy specimen.
Disease-free survival
defined as the time from esophagectomy until evidence of disease recurrence or death in participants received esophagectomy.
Event-free survival
defined as the time from enrollment to an event which may include radiographic progression, clinical progression, local or distant recurrence, second aerodigestive tract squamous cell carcinoma, and death.
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National Taiwan University Hospital
Lead sponsor
BeiGene
Collaborator
