Immunotherapy for Advanced Esophageal Squamous Cell Carcinoma—Renewed Enthusiasm and a Lingering Challenge
Laércio Lopes da Silva, Pedro Nazareth Aguiar, Gilberto Lopes
Abstract
Esophageal cancer is the sixth leading cause of cancerrelated mortality worldwide, with an estimated 544 076 deaths in 2020. The diagnosis typically occurs in patients with locally advanced unresectable or metastatic disease, when palliative chemotherapy is the primary treatment option, and the 5-year survival rates can be as low as 5%. Esophageal adenocarcinoma is the most common among Western populations, occurs most often in the lower esophagus near the gastric junction, and is associated with obesity, gastric reflux, and a precursor state termed Barrett esophagus. Esophageal squamous cell carcinoma occurs predominantly in the upper and mid-esophagus and is associated with smoking and alcohol exposure, although ESCC risk factors among non-Western populations are less known. These histologies differ in risk factors, prognosis, and genetics. 5 Despite ESCC's high incidence, to our knowledge, robust clinical trials are scarce, and most of the evidence guiding its treatment comes from studies assessing ESCC and EAC combined. There has been little progress in treating esophageal cancer over the last 2 decades, with median overall survival (OS) for these patients remaining close to 11 months. he results from ESCORT-1st, published in JAMA, 6 thus represent a welcome new piece of evidence in a critical turning point in the treatment landscape of ESCC. In this large, double-blind, phase 3 clinical trial, Luo and colleagues 6 evaluated the efficacy and safety of camrelizumab (200 mg) vs placebo combined with up to 6 cycles of paclitaxel (175 mg/m 2 , every 3 weeks) plus cisplatin (75 mg/m 2 , every 3 weeks). The authors included 596 patients with unresectable, locally advanced, or metastatic ESCC who had received no systemic therapy for at least 6 months before enrollment. There were 298 participants (median age, 62 years; 87.2% men) randomly assigned to the camrelizumab plus chemotherapy (camrelizumab-chemotherapy) group and 298 participants (median age, 62 years; 88.3% men) allocated to the placebo plus chemotherapy group. ESCORT-1st met its coprimary end points of progression-free survival (PFS) and OS, irrespective of programmed cell death ligand 1 (PD-L1) expression.