Effect of Camrelizumab vs Placebo Added to Chemotherapy on Survival and Progression-Free Survival in Patients With Advanced or Metastatic Esophageal Squamous Cell Carcinoma

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 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.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/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 camrelizumabchemotherapy 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.

Cost-Effectiveness Analysis of Camrelizumab vs. Placebo Added to Chemotherapy as First-Line Therapy for Advanced or Metastatic Esophageal Squamous Cell Carcinoma in China

“…The clinical efficacy and safety data were based on the patients in the ESCORT-1st trial, a randomized, double-blind, placebo-controlled, multicenter, phase 3 trial enrolled patients from 60 hospitals in China ( 11 ). Patients were eligible if they conformed to the following conditions: 1.…”

“…The world’s first phase III clinical trial of the first-line immunotherapy combined with chemotherapy for the advanced ESCC was the ESCORT-1st trial conducted in China, and we performed a cost-effectiveness analysis based on ESCORT-1st trial ( 11 ). The ESCORT-1st trial was conducted to evaluate the efficacy and adverse events of camrelizumab combined with paclitaxel and cisplatin compared with placebo combined with paclitaxel and cisplatin for the first-line treatment of advanced ESCC ( 11 ). Results demonstrated that camrelizumab combined with chemotherapy significantly prolonged median OS (mOS, 15.3 months vs. 12.0 months) and median PFS (mPFS, 6.9 months vs. 5.6 months) compared with placebo plus chemotherapy.…”

Immune-Checkpoint Inhibition in the Treatment of Gastro-Esophageal Cancer: A Closer Look at the Emerging Evidence

“…In this NeoAegis study, with a median follow up of 24.5 months, the second futility analysis reported 143 deaths including 70 and 73 deaths in the CROSS and MAGIC arms, respectively. In the CROSS and MAGIC arms, the 3-year estimated survival probabilities were 56% (95% CI 47-64) and 57% (95% CI [48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65], respectively (HR 1.02; 95% CI 0.74-1.42). Considering that data were notable for non-inferiority, the DSMB recommended closure of recruitment in December 2020 [62].…”

“…The results of the phase 3 ESCORT-1st study which evaluated the efficacy and safety of camrelizumab plus chemotherapy vs. chemotherapy in Asian patients with untreated advanced or metastatic esoSCC irrespective of PD-L1 status were recently presented [ 48 ]. A total of 596 patients were randomized to receive either camrelizumab or placebo, both in combination with paclitaxel and cisplatin for up to 6 cycles.…”

“…With a median follow-up of 10.8 months, camrelizumab plus chemotherapy showed a superior OS benefit (median 15.3 month; 95% CI 12.8–17.3 vs. 12.0 months; 95% CI 11.0–13.3; HR 0.70, 95% CI 0.56–0.88; p = 0.001). Camrelizumab plus chemotherapy was also superior for PFS vs. placebo plus chemotherapy (median 6.9 months; 95% CI 5.8–7.4 vs. 5.6 months; 95% CI 5.5–5.7; HR 0.56, 95% CI 0.46–0.68; p < 0.0001) [ 48 ]. However, the OS differences in each of the PD-L1 < 10%, <5% and <1% subgroups were not statistically significant.…”