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%). Clinical TNM staging, pathologic findings and pathologic remission
No. Pre-treatment clinical TNM staging Post-treatment radiological TNM staging Post-treatment pathological staging Post-treatment residual viable tumor (%) 1 cT2N0M0 ycT2N0M0 ypT3N0M0 90 2 cT2N0M0 ycT2N0M0 ypT1bN0M0 2 3 cT3N0M0 ycT2N0M0 ypT3N0M0 8 4 cT3N0M0 ycT2N0M0 ypT0N0M0 0 5 cT3N0M0 ycT3N0M0 ypT3N0M0 85 6 cT3N0M0 ycT2N0M0 ypT3N0M0 80 7 cT3N0M0 ycT3N0M0 ypT3N0M0 90 8 cT3N0M0 ycT2N0M0 ypT1bN0M0 1 9 cT3N0M0 ycT2N0M0 ypT3N0M0 75 10 cT3N0M0 ycT1N0M0 ypT0N0M0 0 11 cT2N0M0 ycT1N0M0 ypT0N0M0 0 12 cT3N0M0 ycT3N0M0 ypT0N0M0 0 13 cT2N0M0 ycT4N1M0 ypT3N1M0 90 14 cT3N1M0 ycT2N0M0 ypT3N0M0 2 15 cT3N2M0 ycT3N2M0 ypT3N2M0 90
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.
NCT03946969.
Department of Oncology and Cancer Rehabilitation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
National Natural Science Foundation of China (Nos. 81871944) and Jiangsu Province Key Medical Talents (Nos. ZDRCA2016026).
All authors have declared no conflicts of interest.