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.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Wu reported receiving personal fees from AstraZeneca, Roche, Bristol Myers Squibb, MSD, Pfizer, Lilly, Boehringer Ingelheim, Merck, Innovent, and Jiangsu Hengrui Pharmaceuticals Co Ltd. Drs Shen, Yang, and Zou reported being employees of Jiangsu Hengrui Pharmaceuticals Co, Ltd. Dr Xu reported serving as a consultant or an advisor to Bristol Myers Squibb, Merck Serono, Roche, Astellas, and AstraZeneca. No other disclosures were reported.

Figures

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).