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Preoperative Pembrolizumab combined with Chemoradiotherapy for Esophageal Squamous Cell Carcinoma: Trial Design

Open AccessPublished:November 09, 2021DOI:https://doi.org/10.1016/j.xjon.2021.11.003
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      Abstract

      Objective

      The safety and feasibility of preoperative pembrolizumab combined with chemoradiotherapy (PPCT) for resectable esophageal squamous cell carcinoma (ESCC) have been well confirmed by prior PALACE-1 trial. Potential therapeutic benefit was also observed with a pathologic complete response (pCR) rate of 55.6% after PPCT. We conduct this multicenter single-arm PALACE-2 study to investigate the efficacy and to further confirm the safety of PPCT (NCT04435197).

      Methods

      A total of 143 patients with previously untreated, locally advanced, and surgically resectable ESCC (T2-T4a, N0-N+, M0) will be enrolled. 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 PD-L1 expression is not mandatory for enrollment. Patients will receive PPCT, which includes concurrent pembrolizumab (200 mg on day 1 and day 22), carboplatin (AUC=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 endpoint is the rate of pCR. 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 PALACE-1 trial. This subsequent multicenter PALACE-2 study will investigate the efficacy and further confirm the safety of PPCT for locally advanced, resectable ESCC.

      Keywords

      Glossary of Abbreviations:

      AEs (adverse events), CT (computed tomography), ESCC (esophageal squamous cell carcinoma), ICI (immune checkpoint inhibitor), nCRT (neoadjuvant chemoradiotherapy), OS (overall survival), pCR (pathologic complete response), 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)