2962 - A Phase II Clinical Trial of Sintilimab Combined with Lower Dose Neoadjuvant Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma

Y. Liu¹, Y. Chen¹, R. Yu¹, B. Zou¹, X. Zhou¹, Y. Gong¹, F. Peng¹, Y. Hu², W. Wang², Y. Yuan², L. Chen², D. Tian², M. Yu¹, Y. Li¹, and Y. Lu¹; ¹Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University., Chengdu, China, ²Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China., Chengdu, China

Purpose/Objective(s): Neoadjuvant chemoradiotherapy is the standard treatment for resectable locally advanced esophageal squamous cell carcinoma (ESCC). The efficacy and safety of immunotherapy in neoadjuvant therapy for patients with resectable locallyESCC remains debated, and how to maximize the benefits of combination therapies is still unknown. Given the potential of immunotherapy in ESCC, we conducted a study using a lower dose neoadjuvant chemoradiotherapy combined with the PD-1 inhibitor sintilimab to balance therapeutic efficacy and potential side effects. Materials/

Methods: The enrolled patients received 2 courses of chemotherapy with paclitaxel (135mg/m2) and carboplatin (AUC=4), 3 courses of sintilimab treatment, and combined with radiation (30 Gy in 15 fractions) before surgery. The GTV is defined as macroscopic primary tumor (GTVp) and involved lymph nodes (GTVn). Clinical tumor volume (CTV) included the CTV of the primary tumor (CTVp) and metastatic lymph nodes (CTVn). CTVn was defined as the region of positive lymph nodes, and CTVp was 3 cm outward in the head-to-toe direction of the GTVp and 0.5 cm outward for the remainder. PTV was defined as 0.5 cm outward of the CTV. The interval between the last course and the operation was 4 to 6 weeks. The primary endpoint was pathologic complete response (pCR) and the secondary endpoint was treatment-related adverse events. Treatment-related adverse events (TRAEs) were monitored and recorded from the day of neoadjuvant therapy until 90 days after the last dose or 30 days after surgery, the adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE version 5.0).

Results: Of the 18 patients enrolled, 2 patients refused surgery due to improved symptoms after neoadjuvant therapy, and 1 patients were discharged due to side effects. Esophagectomy was performed in 15 patients, R0 resection rate was 100%. The tumor imaginations were obtained at baseline and within a week before surgery, of these cases, 8 (53.3%) achieved partial response (PR) and 7 (46.7%) were evaluated as stable disease (SD). Upon pathologic evaluation, 9 patients (60.0%) achieved the pathologic complete response (pCR), and 3 patients (20.0%) achieved pCR in primary lesion with residual lymph node lesions (ypT0N+). Of the eight patients who achieved PR as assessed by computed tomography (CT), six also attained pCR, and three of the patients who were evaluated as SD also reached pCR. Of the 18 patients enrolled, the incidence of grade 3-4 TRAEs was 55.6%, and the most common grade 3-4 TRAEs was hematotoxicity (9/18, 50%), and one patient experienced grade 3 immune-related hepatitis. Any grade AEs (=20%) were decreased white blood cell count (88.9%), anemia (44.4%), and decreased neutrophil count (66.7%).

Conclusion: The lower dose neoadjuvant chemoradiotherapy combined with the PD-1 inhibitor sintilimab regimen is effective and safe.