175P A study of neoadjuvant sintilimab combined with triplet chemotherapy of lipo-paclitaxel, cisplatin, and S-1 for resectable esophageal squamous cell carcinoma (ESCC)

Although preoperative chemoradiotherapy is the standard of care for patients (pts) with resectable locally advanced esophageal cancer, ESCC still has a dismal prognosis. PD-1 blockade has demonstrated significant clinical benefits in metastatic ESCC (ORIENT-02), and the addition of PD-1 to chemotherapy improved clinical outcomes in other squamous cell malignancies, such as lung and head & neck cancer. This trial (KEEP-G 03) evaluates the feasibility and safety of preoperative sintilimab (anti-PD-1) in combination with triplet chemotherapy in resectable ESCC. This is a single-arm, phase Ib/II trial. Pts with histopathologically confirmed resectable (T1b-T3,N0-N+M0, AJCC 8th) ESCC were enrolled. Sintilimab (200mg, iv, d1) in combination with lipo-paclitaxel (135 mg/m2, iv, d1), cisplatin (25mg/m2, iv, d1-3), S-1 (40mg po, bid, d1-14) were given for 2 cycles every 3wks, followed by esophagectomy. The primary objectives were feasibility and safety (CTCAE 5.0), and secondary objectives included MPR, pCR, R0 rate, RFS, and OS. From 5/2019 to 6/2020, 17 pts were enrolled. The median age was 65 yrs (range 42-69), 76.4% were male, and 70.6% had an ECOG PS 1. The proportions of cT- and cN- stage were T2 23.5%, T3 76.5%, and N0 94.1%, N1 5.9%. All pts completed neoadjuvant treatment and 15 have completed esophagectomy stick to schedule (≤6wks) with 100% R0 resection. 2 pts were waiting for planned surgery at time of abstract. No pts failed to proceed to surgery. And no unexpected surgical complication was observed. Grade 3/4 TRAEs (35.3%) were leukopenia, neutropenia, and anemia. 1 pts experienced grade 1 rash suspicious of immune-related. Of note, 4 out of 15 achieved pCR (26.7%) and 8 achieved MPR (53.3%).Table: 175PClinical TNM staging, pathologic findings and pathologic remissionNo.Pre-treatment clinical TNM stagingPost-treatment radiological TNM stagingPost-treatment pathological stagingPost-treatment residual viable tumor (%)1cT2N0M0ycT2N0M0ypT3N0M0902cT2N0M0ycT2N0M0ypT1bN0M023cT3N0M0ycT2N0M0ypT3N0M084cT3N0M0ycT2N0M0ypT0N0M005cT3N0M0ycT3N0M0ypT3N0M0856cT3N0M0ycT2N0M0ypT3N0M0807cT3N0M0ycT3N0M0ypT3N0M0908cT3N0M0ycT2N0M0ypT1bN0M019cT3N0M0ycT2N0M0ypT3N0M07510cT3N0M0ycT1N0M0ypT0N0M0011cT2N0M0ycT1N0M0ypT0N0M0012cT3N0M0ycT3N0M0ypT0N0M0013cT2N0M0ycT4N1M0ypT3N1M09014cT3N1M0ycT2N0M0ypT3N0M0215cT3N2M0ycT3N2M0ypT3N2M090 Open table in a new tab . Given the encouraging MPR and pCR and favorable tolerability, the regimen of sintilimab plus triplet chemotherapy could be a feasible and safe neoadjuvant option for locally advanced ESCC.