Final analysis of the randomized phase 3 ESCORT-1st trial: Camrelizumab plus chemotherapy as first-line treatment for advanced or metastatic esophageal squamous cell carcinoma.

4055 Background: The ESCORT-1st trial (NCT03691090) was a randomized, double-blind, placebo-controlled, phase 3 trial that aimed to evaluate the efficacy and safety of camrelizumab plus chemotherapy compared to placebo plus chemotherapy in previously untreated patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC). Interim analysis of this trial showed significantly longer overall survival (OS) and progression-free survival (PFS) with camrelizumab plus chemotherapy compared to placebo plus chemotherapy (Luo et al., JAMA, 2021). In this report, we present the final analysis of the efficacy and safety outcomes from the ESCORT-1st study, with an additional 1.5-year follow-up. Methods: A total of 596 eligible patients with previously untreated advanced or metastatic ESCC were randomly assigned in a 1:1 ratio to receive either camrelizumab 200 mg or placebo for up to 2 years, in combination with up to 6 cycles of paclitaxel and cisplatin. All treatments were administered intravenously every 3 weeks. Randomization was stratified based on the presence of liver metastases and previous definitive chemoradiotherapy. The primary endpoints of the study were OS and PFS as assessed by an independent review committee. The data cutoff for this final analysis was April 30, 2022. Results: At the data cutoff, the minimum follow-up period was 24 months, and no patients remained on the study treatment. Among the patients, 214 (71.8%) in the camrelizumab plus chemotherapy group and 250 (83.9%) in the placebo plus chemotherapy group had died. The camrelizumab plus chemotherapy group demonstrated a longer median OS compared to the placebo plus chemotherapy group (15.6 months 95% CI 14.0–18.4 vs 12.6 months 95% CI 11.2–13.8, HR 0.70 95% CI 0.58–0.84; one-sided P<0.0001). The 1-year, 2-year, and 3-year OS rates were 62.4% vs 51.7%, 35.9% vs 23.8%, and 25.6% vs 12.8% in the camrelizumab plus chemotherapy group and the placebo plus chemotherapy group, respectively. The median investigator-assessed PFS was also longer with camrelizumab plus chemotherapy compared to placebo plus chemotherapy (7.6 months 95% CI 6.9–8.3 vs 5.8 months 95% CI 5.6–6.6; HR 0.54 95% CI 0.45–0.65; one-sided P<0.0001). No new safety signals were identified during the extended follow-up period. Conclusions: The extended follow-up of the ESCORT-1st trial reaffirms that camrelizumab plus chemotherapy provides significant and clinically meaningful improvements in OS and PFS compared to placebo plus chemotherapy, with a manageable safety profile for patients with untreated advanced or metastatic ESCC. These findings further support the use of first-line camrelizumab plus chemotherapy as the standard of care for these patients. Clinical trial information: NCT03691090 .