This study aims to compare the efficacy and safety of short-course definitive concurrent chemoradiotherapy plus immunotherapy followed by immunotherapy maintenance versus short-course definitive chemoradiotherapy plus immunotherapy maintenance in the treatment of locally advanced unresectable esophageal squamous cell carcinoma, and to exploratorily identify molecular biomarkers associated with treatment efficacy and toxicity.
The RTOG 8501 trial established definitive chemoradiotherapy (dCRT) as the standard treatment for patients with locally advanced unresectable esophageal cancer. Although long-term survival and even cure have been observed in a subset of patients treated with dCRT, the overall short- and long-term outcomes remain unsatisfactory. For example, the complete response (CR) rate after dCRT is only approximately 25%, most patients eventually experience local recurrence or distant metastasis, and the 5-year overall survival rate is only about 20%. Therefore, there remains a substantial unmet medical need for improving the treatment of patients with locally advanced unresectable esophageal cancer.In patients with unresectable esophageal cancer, several small-sample exploratory studies have investigated the combination of immunotherapy with dCRT. The EC-CRT-001 study preliminarily demonstrated that dCRT combined with toripalimab achieved a CR rate of 62% and a 1-year overall survival rate of 78.4% in patients with locally advanced unresectable esophageal squamous cell carcinoma. A study by Zhao et al. explored induction chemo-immunotherapy followed by concurrent chemoradiotherapy, reporting a 1-year overall survival rate of 88.0% and a 2-year local control rate of 81.7%, which were also superior to those reported in traditional studies of chemoradiotherapy alone. Taken together, these findings suggest that the incorporation of immune checkpoint inhibitors (ICIs) into definitive chemoradiotherapy-based multimodal treatment may improve outcomes in patients with locally advanced unresectable esophageal squamous cell carcinoma.Currently, several large randomized controlled trials, such as RATIONALE 311 and KUNLUN, are ongoing to evaluate the efficacy of immunotherapy maintenance following concurrent chemoradiotherapy compared with placebo. However, the optimal integration strategy of chemoradiotherapy and immunotherapy remains unclear. In lung cancer, the PACIFIC trial established the cornerstone role of immunotherapy maintenance in patients with unresectable stage III disease. In esophageal cancer, other studies such as SKYSCRAPER-07 are also investigating the efficacy and safety of immunotherapy maintenance following definitive chemoradiotherapy. Nevertheless, which combination strategy of conventional chemoradiotherapy and ICIs can best balance efficacy and toxicity remains to be elucidated and warrants further clinical investigation.Based on this background, the present study aims to investigate and compare the efficacy and safety of short-course definitive concurrent chemoradiotherapy plus immunotherapy followed by immunotherapy maintenance versus short-course definitive chemoradiotherapy plus immunotherapy maintenance in patients with locally advanced unresectable esophageal squamous cell carcinoma, and to exploratorily identify molecular biomarkers associated with treatment efficacy and toxicity.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
98
This study aims to compare the efficacy and safety of two novel treatment strategies-short-course definitive chemoradiotherapy combined with adjuvant camrelizumab, and short-course definitive chemoradiotherapy combined with concurrent plus adjuvant camrelizumab-in patients with locally advanced unresectable esophageal squamous cell carcinoma.
Jiangsu Cancer Hospital /Jiangsu Institute of Cancer Research
Nanjing, Jiangsu, China
RECRUITING1-year Progression- Free Survival
1-year progression-free survival (PFS) defined as the probability from study enrollment to tumor progression (in any aspect) or death from any cause within 1 year.
Time frame: from study enrollment to tumor progression (in any aspect) or death from any cause within 1 year.
complete response rate
Complete response rate at 3 months after completion of radiotherapy: assessed by CT, high-resolution MRI and/or PET-CT, in combination with endoscopic ultrasound-guided bite-on-bite biopsy.
Time frame: 3 months after completion of radiotherapy
treatment-related adverse events
Grade ≥3 treatment-related adverse events will be recorded according to CTCAE version 5.0 during the treatment period, from study enrollment until 90 days after the final administration of chemoradiotherapy.
Time frame: from study enrollment until 90 days after the final administration of chemoradiotherapy
Overall Survival
Defined as from date of enrollment until the date of death from any cause or the date of last follow-up, whichever came first, assessed up to 100 months
Time frame: From study enrollment to death from any cause, assessed up to 100 months
Duration of Response
From the time of first response to disease progression or death from any cause, whichever came first, assessed up to 100 months
Time frame: From the time of first response to disease progression or death from any cause, whichever came first, assessed up to 100 months
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