Preoperative treatment for potentially resectable esophageal cancer: Insights from a nationwide real-world study.

Abstract

e14598 Background: In the ASTRUM-007 trial, serplulimab combined with chemotherapy significantly prolonged overall survival (OS) in patients with advanced esophageal cancer (EC). Despite these encouraging results, evidence regarding its efficacy and safety in the neoadjuvant setting remains absent. This nationwide real-world study evaluates the efficacy and safety of serplulimab-based neoadjuvant therapy in EC, addressing the anti-tumor activity and clinical feasibility. Methods: This nationwide, real-world, observational study was led by the First Affiliated Hospital, Zhejiang University School of Medicine and conducted across nine centers in China. This analysis included patients with histologically confirmed esophageal cancer who received serplulimab-based neoadjuvant therapy followed by radical surgery. Pathologic complete response (pCR), major pathologic response (MPR), the R0 resection rate, radiographic response during neoadjuvant treatment, and adverse events (AEs) were analyzed. Results: Between March 2022 and December 2023, a total of 95 EC patients who received serplulimab-based neoadjuvant therapy followed by radical surgery were included. The majority were male (n = 86, 90.53%), with a median age of 63 years, and 37 patients (38.95%) were aged ≥65 years. SCC accounted for 93 cases (97.89%) of the primary tumors, with most located in the middle thoracic esophagus (n = 68, 71.58%). Patients generally presented with heavy tumor burden, with 88 patients (92.63%) at stage T3/4 and 90 patients (94.74%) with positive lymph nodes. Of the 95 patients enrolled in the study, 89 underwent R0 resection, resulting in an R0 rate of 93.68%. The pCR rate was 23.16%, and the MPR rate was 41.05%. Tumor and nodal downstaging rates were 56.84% and 61.05%, respectively. Logistic regression showed that PD-L1-positive patients had significantly higher odds of achieving pCR (OR = 12.73, P = 0.016) and MPR (OR = 2.95, P = 0.031). Among 69 patients with measurable baseline lesions who underwent at least one radiological evaluation after initiating neoadjuvant therapy, 31 patients achieved partial response (PR) as the best response, resulting in an overall response rate (ORR) of 44.93% (95% CI: 32.92%–57.38%). The overall AE incidence was 96.84%, with 28.42% experiencing grade ≥3 AEs. The most common grade ≥3 AE was pneumonia, which occurred in 22.11% of patients. No new safety signals were identified, and patients generally tolerated the treatment well. Conclusions: This study represents the largest nationwide real-world investigation of serplulimab-based neoadjuvant therapy for esophageal cancer in China. The findings highlight the potential of serplulimab-based neoadjuvant therapy in transforming unresectable esophageal tumors into resectable disease with manageable toxicity.