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

Abstract

Importance: Standard 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.

Objective: To 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 participants: This 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.

Interventions: Patients 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/m2) and cisplatin (75 mg/m2). All treatments were given intravenously every 3 weeks.

Main outcomes and measures: Coprimary end points were overall survival (significance threshold, 1-sided P < .02) and progression-free survival (significance threshold, 1-sided P < .005).

Results: Of 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 relevance: Among 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 registration: ClinicalTrials.gov Identifier: NCT03691090.

Figure 1.. Assessment, Randomization, and Flow in a Trial of Camrelizumab in the Treatment of Esophageal Squamous Cell Carcinoma

^aSee Table 2 in Supplement 2 for detailed reasons. ^bPatients were randomized in a 1:1 ratio stratified by liver metastases (yes vs no) and previous definitive chemoradiation (yes vs no).

Figure 2.. Kaplan-Meier Estimates of Overall Survival and Progression-Free Survival per Independent Review Committee

The tick marks indicate censored individuals. The median follow-up duration was 10.8 months (interquartile range, 7.3-14.3 months). A, There were 135 deaths (45.3%) in the camrelizumab-chemotherapy group and 174 (58.4%) in the placebo-chemotherapy group, with median overall survival of 15.3 months (95% CI, 12.8-17.3) and 12.0 months (95% CI, 11.0-13.3), respectively. B, There were 199 events (66.8%) of disease progression or death in the camrelizumab-chemotherapy group and 229 (76.8%) in the placebo-chemotherapy group, with median progression-free survival of 6.9 months (95% CI, 5.8-7.4) and 5.6 months (95% CI, 5.5-5.7), respectively.

Figure 3.. Health-Related Quality of Life

A total of 298 patients in camrelizumab-chemotherapy group and 298 patients in placebo-chemotherapy group were included in the quality-of-life assessment. See the Methods section for calculating scores. A, A high score based on the European Organization for Research and Treatment of Cancer (EORTC) quality of life core 30 (QLQ-C30) scale for the global health status and functional scale indicates good condition. B, A high score for the constitutional cancer symptom scale or item of QLQ-C30 indicates a worse condition. C, A high score in the esophageal cancer–specific symptom scale or item from QLQ esophageal cancer 18 (QLQ-OES18) indicates a worse condition. Detailed descriptions of quality of life are provided in statistical analysis plan. Error bars indicate (95% CIs).