148P - Neoadjuvant camrelizumab plus metronomic chemotherapy in patients with advanced esophageal squamous cell carcinomas: A randomized phase II trial

Background

Metronomic chemotherapy (MCT) has been shown to preserve immune function, presenting a potential combination strategy with PD-1-based immunotherapy to exert synergistic effects. However, its efficacy in the neoadjuvant setting for advanced ESCC requires further clinical clarification.

Methods

This study reports the first phase II, single-center, randomized clinical trial comparing the efficacy and safety of neoadjuvant MCT plus the PD-1 inhibitor camrelizumab versus MCT alone in untreated, resectable (stages II or III) ESCC patients.A total of 30 eligible patients were randomly assigned to two groups: one receiving MCT with the recipe of paclitaxel cisplatin and 5-fluorouracil weekly for six weeks (MCT group), and the other receiving the same MCT regimen in combination with camrelizumab (200 mg on D1 and D22) (IO+MCT group). Surgical resection occurred approximately 3-4 weeks later.

Results

Both neoadjuvant therapies exhibited acceptable side effects and satisfactory tolerability. Ultimately, 24 patients (13 in the MCT group and 11 in the IO+MCT group) successfully underwent R0 resection. The primary study endpoints included pathological complete response (pCR) and major pathological response (MPR) rates for the two groups, which were 15.4% versus 54.5% and 53.8% versus 81.8%, respectively. The 2-year DFS and OS rates were 73% and 85% for the MCT group, and73% and 91% for the IO+MCT group. Mechanistic insights were obtained using digital spatial profiling, multiplex immunofluorescent staining and bulk RNA sequencing. IO+MCT treatment effectively reprogrammed the tumor microenvironment, reduced T cell exhaustion, and promoted tertiary lymphoid structure formation. Non-pCR patients in the IO+MCT group showed higher expression of mitochondria-related genes, correlating with increased T cell exhaustion and hypoxia scores.

Conclusions

In conclusion, the neoadjuvant camrelizumab plus MCT significantly improved pCR rates in ESCC patients offering substantial benefits for patients.

Clinical trial identification

ChiCTR2000039638.

Legal entity responsible for the study

The authors.

Funding

National Natural Science Foundation of China.

Disclosure

All authors have declared no conflicts of interest.