Preoperative pembrolizumab combined with chemoradiotherapy for esophageal squamous cell carcinoma: Trial design

Yuyan Zheng, Chengqiang Li, Bentong Yu, Shengguang Zhao, Jian Li, Xiaoyan Chen, Hecheng Li, Yuyan Zheng, Chengqiang Li, Bentong Yu, Shengguang Zhao, Jian Li, Xiaoyan Chen, Hecheng Li

Abstract

Objective: The safety and feasibility of preoperative pembrolizumab combined with chemoradiotherapy (PPCT) for resectable esophageal squamous cell carcinoma have been confirmed by the prior Preoperative Anti-PD-1 Antibody combined with Chemoradiotherapy for Locally Advanced Squmous Cell Carcinoma of Esophageus (PALACE)-1 trial. Potential therapeutic benefit was also observed with a pathologic complete response rate of 55.6% after PPCT. We will conduct the multicenter single-arm PALACE-2 study to investigate the efficacy and to further confirm the safety of PPCT (ClinicalTrials.gov ID: NCT04435197).

Methods: A total of 143 patients with previously untreated, locally advanced, and surgically resectable esophageal squamous cell carcinoma (T2 through T4a, N0 through N+, M0) will be enrolled in PALACE-2. Main exclusion criteria are autoimmune disease, interstitial lung disease, ongoing immunosuppressive therapy, and having received chemotherapy, radiotherapy, target therapy, or immune therapy for this or any other malignancies. Positive programmed cell death ligand 1 expression is not mandatory for enrollment. Patients will receive PPCT, which includes concurrent pembrolizumab (200 mg on day 1 and day 22), carboplatin (area under the curve = 2, once a week for 5 weeks), nab-paclitaxel (50 mg/m2, once a week for 5 weeks), and radiotherapy (23 fractions of 1.8 Gy, 5 fractions a week). Esophagectomy will be performed within 4 to 6 weeks after the completion of PPCT.

Results: The primary end point is the rate of pathologic complete response. Secondary outcome measures are 3-year disease-free survival rate, 3-year overall survival rate, R0 resection rate, and adverse events during neoadjuvant and perioperative periods.

Conclusions: PPCT was preliminarily demonstrated to be safe, feasible, and to provide potential therapeutic benefits by the PALACE-1 trial. The subsequent multicenter PALACE-2 study will investigate the efficacy and further confirm the safety of PPCT for locally advanced, resectable esophageal squamous cell carcinoma.

Keywords: AEs, adverse events; CROSS, Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study; CT, computed tomography; ESCC, esophageal squamous cell carcinoma; ICI, immune checkpoint inhibitor; OS, overall survival; PALACE, Preoperative Anti-PD-1 Antibody combined with Chemoradiotherapy for Locally Advanced Squmous Cell Carcinoma of Esophageus; PD-1, programmed cell death protein 1; PD-L1, programmed cell death ligand 1; PET-CT, positron emission tomography-computed tomography; PPCT, preoperative pembrolizumab combined with chemoradiotherapy; chemoradiotherapy; esophageal squamous cell carcinoma; immunotherapy; nCRT, neoadjuvant chemoradiotherapy; neoadjuvant therapy; pCR, pathologic complete response.

© 2021 The Author(s).

Figures

Graphical abstract
Graphical abstract
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/9390428/bin/fx2.jpg
Flowchart of the PALACE-2 trial.
Figure 1
Figure 1
Flowchart of the Preoperative Anti-PD-1 Antibody combined with Chemoradiotherapy for Locally Advanced Squmous Cell Carcinoma of Esophageus-2 trial. ESCC, Esophageal squamous cell carcinoma; AUC, area under the curve; PET-CT, positron emission tomography-computed tomography.
Figure 2
Figure 2
Trial design and flow chart of the Preoperative Anti-PD-1 Antibody combined with Chemoradiotherapy for Locally Advanced Squmous Cell Carcinoma of Esophageus-2 trial. ESCC, Esophageal squamous cell carcinoma; AUC, area under the curve; pCR, pathologic complete response; DFS, disease-free survival; OS, overall survival; AEs, adverse events.
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/9390428/bin/fx3.jpg

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