Abstract 5230: Neoadjuvant programmed cell death protein 1 inhibitors combined with chemotherapy in resectable esophageal squamous carcinoma: an open-label, single-arm study

Abstract

Abstract Objective: 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 neoadjuvant PD-1 inhibitors in combination with chemotherapy for resectable ESCC. Methods: All patients had treatment-naïve resectable ESCC (stage III) that were confirmed by histopathology. All patients were scheduled to receive surgery within 4-6 weeks after neoadjuvant treatment (2 cycles) consisting of PD-1 inhibitors (Camrelizumab 200mg or Sintilimab 200 mg or Tislelizumab 200 mg) combined with two conventional chemotherapy regimens (Cisplatin + paclitaxel). The primary endpoint was the major pathologic response (MPR). Secondary endpoints were disease-free survival (DFS), R0 resection rate and safety profile. Immune signature of immune cells were evaluated in surgical specimens using immunofluorescence. Results: Between Aug. 1, 2020, and Oct. 1, 2021, we assessed 10 patients for screening, of whom 10 patients were enrolled. Neoadjuvant therapy was not associated with delays in surgery or increased surgical complications/mortality. The median follow-up was 5.0 months (range 2.0∼31.0 months). Ten (100.0%) successfully underwent R0 resection. Of the 10 evaluable patients, 6 (60.0%) were MPR, 4 (40.0%) were pathologic complete response (pCR). Imaging evaluation was feasible in all patients. Partial response (PR) was achieved in 1 (10.0%) and stable disease (SD) was observed in 8 (80.0%). The most common treatment-related grade 1-2 adverse events were anemia (5, 50.0%), nausea (3, 30.0%), vomiting (3, 30.0%), constipation (2, 20.0%) and myelosuppression (2, 20.0%). There was no grade 3-4 events and treatment-related deaths. The presence of CD3+ T cells, B cell, and CD56 bright were statistically comparable patient groups of MPR and pCR, with an increased tendency in pCR patients. In addition, macrophages, CD8+ T cells, PD-1+CD8+ T cell, Treg cells, and PD-L1+CD68+ cells in pCR patients showed a downward trend. Conclusions: Neoadjuvant PD-1 inhibitors plus chemotherapies had manageable treatment-related toxic effects. This regimen induced pCR or MPR in 100.0% of resected tumor, demonstrating its antitumor efficacy in resectable ESCC. Citation Format: Bo Jiang, Xin Yang, Junling Zhang, Mengli Huang. Neoadjuvant programmed cell death protein 1 inhibitors combined with chemotherapy in resectable esophageal squamous carcinoma: an open-label, single-arm study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5230.