1378P A single-center, prospective, open-label, single-arm trial of sintilimab with paclitaxel and carboplatin as a neoadjuvant therapy for esophageal squamous carcinoma

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Although neoadjuvant chemotherapy has been recommended for resectable ESCC patients, the 5-year overall survival rate was less than 50%. Immune checkpoint inhibitors have been shown to be efficient for advanced ESCC, while few studies focus on the neoadjuvant immunotherapy combined with chemotherapy. Herein, we designed a trial to evaluate the safety and efficacy of Sintilimab combined with paclitaxel and carboplatin for resectable ESCC. All patients had treatment-naïve resectable ESCC (stage II-ⅣA) that were confirmed by histopathology. Each patient received 2 cycles of combined therapy with sintilimab (200 mg), paclitaxel (135 mg/m2) and carboplatin (area under the curve = 5). The primary endpoint was the major pathologic response (MPR). Secondary endpoints were disease-free survival (DFS), overall survival (OS), R0 resection rate and safety profile. Between Oct. 1, 2019, and Apr. 1, 2021, we assessed 45 patients for screening, of whom 40 patients were enrolled. Neoadjuvant therapy was not associated with delays in surgery or increased surgical complications/mortality. The median follow-up was 7.7 months (range 2.0∼21.0 months). The 6-month local RFS and 6-month OS were 92.5% and 97.5%, respectively. Thirty-nine (97.5%) successfully underwent R0 resection. Of the 40 evaluable patients, 19 (47.5%) were MPR, 10 (25.0%) were pathologic complete response (pCR). Imaging evaluation was feasible in all 40 patients. Partial response (PR) was achieved in 33 (82.5%) and stable disease (SD) was observed in 7 (17.5%). The most common treatment-related grade 1-2 adverse events were thrombocytopenia (8, 20.0%), anemia (19, 47.5%), myelosuppression (6, 15.0%), appetite loss (10, 25%), hair loss (12, 30%) and liver dysfunction (3, 7.5%). The most frequent grade 3-4 events were myelosuppression (3, 7.5%), neutropenia (4, 10.0%), thrombocytopenia (1, 2.5%) and severe anemia (1, 2.5%). There was treatment-related deaths. Neoadjuvant sintilimab plus paclitaxel and carboplatin had manageable treatment-related toxic effects. This regimen induced pCR or MPR in 81.2% of resected tumor, demonstrating its antitumor efficacy in resectable ESCC.