Effect Of Camrelizumab Vs Placebo Added To Chemotherapy On Survival And Progression-Free Survival In Patients With Advanced Or Metastatic Esophageal Squamous Cell Carcinoma: The Escort-1st Randomized Clinical Trial

Key PointsQuestionDoes the addition of camrelizumab to chemotherapy improve outcomes when used as first-line treatment for patients with advanced or metastatic esophageal squamous cell carcinoma? FindingsIn this randomized clinical trial that included 596 patients with advanced or metastatic esophageal squamous cell carcinoma, camrelizumab combined with chemotherapy, compared with placebo and chemotherapy, significantly improved overall survival (15.3 vs 12.0 months, respectively; hazard ratio for death, 0.70) and progression-free survival (6.9 vs 5.6 months, respectively; hazard ratio for disease progression or death, 0.56). MeaningAmong patients with advanced or metastatic esophageal squamous cell carcinoma, an initial treatment strategy of camrelizumab combined with chemotherapy, compared with placebo and chemotherapy, resulted in improved overall survival and progression-free survival.ImportanceStandard first-line therapy for advanced or metastatic esophageal carcinoma is chemotherapy, but the prognosis remains poor. Camrelizumab (an anti-programmed death receptor 1 [PD-1] antibody) showed antitumor activity in previously treated advanced or metastatic esophageal squamous cell carcinoma. ObjectiveTo evaluate the efficacy and adverse events of camrelizumab plus chemotherapy vs placebo plus chemotherapy as a first-line treatment in advanced or metastatic esophageal squamous cell carcinoma. Design, Setting, and ParticipantsThis randomized, double-blind, placebo-controlled, multicenter, phase 3 trial (ESCORT-1st study) enrolled patients from 60 hospitals in China between December 3, 2018, and May 12, 2020 (final follow-up, October 30, 2020). A total of 751 patients were screened and 596 eligible patients with untreated advanced or metastatic esophageal squamous cell carcinoma were randomized. InterventionsPatients were randomized 1:1 to receive either camrelizumab 200 mg (n=298) or placebo (n=298), combined with up to 6 cycles of paclitaxel (175 mg/m(2)) and cisplatin (75 mg/m(2)). All treatments were given intravenously every 3 weeks. Main Outcomes and MeasuresCoprimary end points were overall survival (significance threshold, 1-sided P<.02) and progression-free survival (significance threshold, 1-sided P<.005). ResultsOf the 596 patients randomized (median age, 62 years [interquartile range, 56-67 years]; 523 men [87.8%]), 1 patient in the placebo-chemotherapy group did not receive planned treatment. A total of 490 patients (82.2%) had discontinued the study treatment. The median follow-up was 10.8 months. The overall survival for the camrelizumab-chemotherapy group was a median of 15.3 months (95% CI, 12.8-17.3; 135 deaths) vs a median of 12.0 months (95% CI, 11.0-13.3; 174 deaths) for the placebo-chemotherapy group (hazard ratio [HR] for death, 0.70 [95% CI, 0.56-0.88]; 1-sided P=.001). Progression-free survival for camrelizumab plus chemotherapy was a median of 6.9 months (95% CI, 5.8-7.4; 199 progression or deaths) vs 5.6 months (95% CI, 5.5-5.7; 229 progression or deaths) for the placebo-chemotherapy group (HR for progression or death, 0.56 [95% CI, 0.46-0.68]; 1-sided P<.001). Treatment-related adverse events of grade 3 or higher occurred in 189 patients (63.4%) in the camrelizumab-chemotherapy group and 201 (67.7%) in the placebo-chemotherapy group, including treatment-related deaths among 9 patients (3.0%) and 11 patients (3.7%), respectively. Conclusions and RelevanceAmong patients with advanced or metastatic esophageal squamous cell carcinoma, the addition of camrelizumab to chemotherapy, compared with placebo and chemotherapy, significantly improved overall survival and progression-free survival. Trial RegistrationClinicalTrials.gov Identifier: NCT03691090This clinical trial compares overall and progression-free survival of patients with advanced or metastatic esophageal squamous cell carcinoma randomized to camrelizumab plus chemotherapy or to placebo plus chemotherapy.