Nature Communications | Camrelizumab combined with chemotherapy as preoperative treatment for resectable esophageal squamous cell carcinoma

This study compared the efficacy and safety of Camrelizumab combined with chemotherapy versus preoperative chemoradiotherapy in patients with resectable locally advanced esophageal squamous cell carcinoma. The results demonstrated that the pathological complete response rate of Camrelizumab combined with chemotherapy was comparable to that of preoperative chemoradiotherapy, with superior safety, offering a novel preoperative treatment strategy for patients with resectable esophageal squamous cell carcinoma.

 

Literature Overview
This article, titled 'Camrelizumab plus chemotherapy versus chemoradiotherapy as neoadjuvant therapy for resectable esophageal squamous cell carcinoma: Phase 2 randomized trial (REVO)', published in the journal Nature Communications, reviewed and summarized the efficacy and safety of Camrelizumab combined with chemotherapy versus preoperative chemoradiotherapy in patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC). The study results showed that the pathological complete response (pCR) rate with Camrelizumab combined with chemotherapy was comparable to that of preoperative chemoradiotherapy, while significantly reducing the incidence of ≥ grade 3 treatment-related adverse events. The study further analyzed disease-free survival (DFS) and overall survival (OS) in both patient groups, providing new reference evidence for treatment strategies in locally advanced ESCC.

Background Knowledge
Esophageal squamous cell carcinoma (ESCC) is a highly aggressive tumor, particularly prevalent in East Asia. Preoperative chemoradiotherapy is currently the standard treatment for locally advanced resectable ESCC; however, its clinical application has certain limitations, such as higher adverse reactions and limited accessibility of radiotherapy equipment. In recent years, immune checkpoint inhibitors combined with chemotherapy have garnered increasing attention in the neoadjuvant setting. Camrelizumab, a PD-1 inhibitor already approved for the treatment of advanced ESCC, was evaluated in this multicenter, randomized, open-label Phase 2 clinical trial (REVO) for its non-inferiority and safety compared with preoperative chemoradiotherapy. The study enrolled 104 patients with locally advanced resectable ESCC, randomly assigned to either the Camrelizumab combined chemotherapy group or the preoperative chemoradiotherapy group. The primary endpoint was the pathological complete response rate, with secondary endpoints including major pathological response rate, R0 resection rate, disease-free survival (DFS), overall survival (OS), and adverse events. Study results indicated that the pCR rate in the Camrelizumab combined therapy (ICT) group was 32.7%, comparable to 34.6% in the chemoradiotherapy (CRT) group. Importantly, the safety profile of the ICT group was superior, with a significantly lower incidence of ≥ grade 3 adverse events compared with CRT (19.2% vs. 33.3%). Additionally, both groups achieved an R0 resection rate of 100%, though the ICT group had a lower rate of postoperative complications. These findings suggest that Camrelizumab combined with chemotherapy is non-inferior to preoperative chemoradiotherapy in terms of pCR rate and offers improved safety, presenting a potential treatment option for patients with locally advanced ESCC.

 

 

Research Methods and Experiments
This study was a multicenter, randomized, open-label, Phase 2 non-inferiority clinical trial (REVO, NCT05007145) comparing Camrelizumab combined with chemotherapy (ICT) to preoperative chemoradiotherapy (CRT) in patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC). A total of 104 patients were randomized 1:1 to either the ICT group (Camrelizumab, nab-paclitaxel, cisplatin) or CRT group (nab-paclitaxel, cisplatin, radiotherapy). The primary endpoint was the pathological complete response (pCR) rate; secondary endpoints included major pathological response (MPR) rate, R0 resection rate, disease-free survival (DFS), and overall survival (OS). The study also evaluated treatment-related adverse events (TRAEs) and postoperative complications. Patient baseline characteristics, number of chemotherapy cycles, and radiation dose (CRT group) were recorded and analyzed.

Key Conclusions and Perspectives

• The pCR rate in the Camrelizumab combined chemotherapy group was 32.7% (17/52), versus 34.6% (18/52) in the preoperative chemoradiotherapy group. The lower 90% confidence interval limit for the difference in pCR rates between the two groups did not meet the non-inferiority threshold of 0.5, indicating that ICT was non-inferior to CRT in terms of pCR rate.
• The MPR rate in the ICT group was 42.3% (22/52), versus 57.7% (30/52) in the CRT group. However, both groups achieved an R0 resection rate of 100%.
• At 1-year follow-up, the DFS rate in the ICT group was 89.1%, versus 78.2% in the CRT group. The 1-year OS rate was 100% in the ICT group versus 92.3% in the CRT group, suggesting potential survival benefits with ICT.
• The incidence of ≥ grade 3 TRAEs was significantly lower in the ICT group (19.2%, 10/52) compared with the CRT group (33.3%, 17/51), indicating superior safety with ICT.
• The postoperative complication rate was 31.1% (14/45) in the ICT group and 35.9% (14/39) in the CRT group. Notably, the CRT group had a higher rate of 30-day postoperative mortality (5.1%).

Research Significance and Prospects
This study is the first multicenter, randomized Phase 2 trial comparing ICT and CRT in locally advanced resectable ESCC, providing preliminary evidence supporting ICT as a viable neoadjuvant strategy. Although the sample size is small and long-term survival data are not yet mature, ICT demonstrated non-inferiority in terms of pCR rate and improved safety, offering promising options for clinical application. Further large-scale, long-term follow-up Phase 3 trials are warranted to validate the clinical value of this approach.

 

 

Conclusion
In summary, this multicenter, randomized, open-label Phase 2 clinical trial (REVO) evaluated the efficacy and safety of Camrelizumab combined with chemotherapy (ICT) versus preoperative chemoradiotherapy (CRT) in patients with locally advanced resectable ESCC. The pCR rate for ICT was 32.7%, comparable to 34.6% in the CRT group, while the safety profile of ICT was significantly better, with a lower rate of ≥ grade 3 TRAEs (19.2% vs. 33.3%). The ICT group also showed improved 1-year DFS and OS rates, lower postoperative complication rates, and no 30-day mortality. These findings indicate that ICT maintains non-inferior efficacy while significantly reducing toxicity, offering a safer preoperative treatment strategy for resectable ESCC patients. Further Phase 3 trials are required to confirm long-term survival benefits and explore broader clinical applications.

 

Peiyuan Wang, Yujie Chen, Feng Wang, Shuoyan Liu, and Jiancheng Li. Camrelizumab plus chemotherapy versus chemoradiotherapy as neoadjuvant therapy for resectable esophageal squamous cell carcinoma: Phase 2 randomized trial (REVO). Nature Communications.