A phase 2 study of modified chemotherapy plus pembrolizumab as perioperative therapy for stage II/IIIA esophageal squamous cell carcinoma.

Abstract

e16081 Background: Immunotherapy plus chemotherapy has shown benefits for locally advanced esophageal squamous cell carcinoma (ESCC). However, the optimal dose, administration interval, and sequence between chemotherapy and immune checkpoint inhibitor are still elusive. In this study, we prospectively analyzed the efficacy and safety of modified chemotherapy followed by anti-programmed cell death protein 1 as perioperative therapy for stage II/IIIA ESCC. Methods: Patients with stage II/IIIA esophageal squamous cell carcinoma were eligible for this study. The patients were treated with 2 cycles of attenuated nab-paclitaxel and cisplatin (180-220mg/m2 for nab-paclitaxel, 60 mg/m2 for cisplatin) on day one and pembrolizumab (200 mg for patients weighted ≥60kg or 100 mg for patients weighted <60kg) delayed on day five every 3 weeks. Subsequently, the patients received surgery four to six weeks after the second cycle treatment followed by 2 more cycles of treatments. The primary endpoints were major pathological response rate (MPR), and the second endpoints were pathological complete response rate (pCR), DFS, safety, R0 resection rate, and OS. The last follow-up time was January 31st, 2023. Results: A total of 23 patients were enrolled in our study and received whole 4 cycles of perioperative treatment. Of the whole patients, the mean age was 57.5. The median follow-up time was 19.2 months (range: 4.1-30.1). All patients underwent surgery and received R0 resection after 2 cycles of neoadjuvant attenuated chemotherapy plus delayed pembrolizumab. Down-stage was achieved in 9 of 21 (42.8%) patients with confirmed stage pre- and post- surgery. The MPR rate was 43.5%, and pCR rate was 26.1%. Up to the last follow-up, 1 patient reported death due to brain metastases, and 4 patients experienced disease progression. The median DFS and OS were not reached. The rates of one-year DFS and OS were 88.2% (15/17) and 94.4% (17/18) respectively. 21 patients (95.5%) reported treatment-related adverse events (TRAEs), most of which were grade 1-2. Two patients reported grade 3 leukopenia, and 1 patient reported grade 4 elevated transaminases and discontinued immunotherapy after surgery. The most common TRAEs were nausea (59.1%), rash (36.4%), asthenia or fatigue (31.8%), and leukopenia (27.3%). Conclusions: Our study suggested that modified nab-paclitaxel and cisplatin followed by delayed pembrolizumab as perioperative treatment was effective and well tolerated for locally advanced ESCC. Clinical trial information: ChiCTR2000034925 . [Table: see text]