1540P - Tislelizumab combined with neoadjuvant chemoradiotherapy for resectable locally advanced oesophageal squamous cell carcinoma: A prospective, phase II clinical study

Background

Neoadjuvant chemoradiotherapy (nCRT) is a standard treatment for resectable locally advanced oesophageal squamous cell carcinoma (ESCC); however, its effectiveness is curtailed by recurrence and distant metastasis. Developing novel therapies, such as combined checkpoint inhibitors, is crucial for improving patient survival. Tislelizumab, an anti-PD-1 monoclonal antibody, has shown promise in various malignancies. This is the first phase II study to assess the efficacy and safety of Tislelizumab combined with nCRT for resectable locally advanced ESCC.

Methods

All subjects underwent nCRT with a 40 Gy total radiation dose given daily for 5 days/week. Paclitaxel albumin (taxanes) with cisplatin/carboplatin were given on days 1 and 22, while Tislelizumab was administered twice on days 8 and 29 concurrently with radiation therapy. Finally, surgery was performed at 6-8 weeks post-treatment.

Results

By April 2023, 26 patients were enrolled in the study, with 21 undergoing surgical resection at a 100% R0 resection rate. Patients who received Tislelizumab combined with nCRT achieved a 100% objective remission rate, with 9 (42.8%) patients had complete response rate and 14 (66.6%) patients achieved major pathologic response, no surgical delay, among 6 patients continue to receive postoperative adjuvant therapy. Common side-effects included leukopenia, thrombocytopenia, neutropenia, anemia, anastomotic leakage, and rash. Most adverse events were grades 1/2, and grades 3/4 adverse events include four cases of grade 3 leukopenia, and one case of grade 3 neutropenia. Regrettably, 2 patients have passed away due to the novel coronavirus. The analysis of survival was immature, and patients are still being followed up.

Conclusions

Tislelizumab in combination with nCRT is a safe and effective treatment strategy for resectable locally advanced ESCC. The high complete response rate and favorable safety profile observed in this study warrant further investigation in larger, randomized controlled trials to confirm the benefit of Tislelizumab in improving treatment outcomes for patients with locally advanced ESCC.

Clinical trial identification

CTR2100051599.

Editorial acknowledgement

The drug was kindly provided by Beigene and Kelun.

Legal entity responsible for the study

The authors.

Funding

Clinical Research Incubation Project, West China Hospital, Sichuan University; Science and Technology Department of Sichuan Province; Beijing Medical Award Foundation; the 1·3·5 project for disciplines of excellence; National Natural Science Foundation of China.

Disclosure

All authors have declared no conflicts of interest.