A phase II trial of preoperative chemoradiotherapy and pembrolizumab for locally advanced esophageal squamous cell carcinoma (ESCC).

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4027 Background: Even though preoperative chemoradiotherapy (CRT) showed survival improvement in patients with resectable ESCC in a randomized trial over upfront surgery, ESCC still has a dismal prognosis. With the potential benefit of combining PD-1 blockade to CRT, we conducted a phase II trial which assessed the efficacy, feasibility, and safety of the combination of preoperative CRT and pembrolizumab (PEM) in ESCC. Methods: Patients (pts) with histologically confirmed ESCC (clinical stage Ib to III according to the American Joint Committee on Cancer 7th staging system) were enrolled. Pts received concurrent neoadjuvant chemotherapy (weekly paclitaxel and carboplatin), radiotherapy (44.1 Gy in 21 fractions), and PEM (every 3 week, 200 mg) during 5 weeks followed by surgery. After surgery, pts were treated with PEM during 2 years or until progression, unacceptable toxicity, death, or pts’ refusal, which came first. The primary endpoint was pathologic complete response (pCR) rate in the primary tumor and secondary endpoints were overall survival (OS), disease-free survival (DFS), the incidence of adverse events, and etc. Results: In a total of 28 enrolled pts (median age 60), 26 pts received esophagectomy. Two pts did not undergo surgery due to death (hematemesis) and consent withdrawal. There were two in-hospital mortality cases after surgery, which were resulted from acute lung injury. The pCR in primary tumor was achieved in 46.1% of pts who underwent resection (95% CI: 28.8 – 64.6). With a median follow-up of 11.7 months, median OS was not reached. Six-month and 12-month OS rates were 89.3% and 82.1%, respectively. There was a trend toward better DFS in the pCR group (n = 12) compared with the non-pCR group (n = 14) (HR = 0.33, p = 0.1). Most common treatment-related adverse events were neutropenia (50.0%) and liver enzyme elevation (30.8%) in the neoadjuvant and adjuvant period, respectively. Conclusions: The addition of PEM to preoperative CRT in ESCC demonstrated promising efficacy with acceptable toxicity. Based on the results, further investigation is warranted in a phase III clinical trial. The exploratory endpoints including biomarkers analyses are ongoing. Clinical trial information: NCT02844075.