Abstract
BackgroundAim to establish the inhibitors of programmed cell death protein 1 (PD-1) as second-line therapy for advanced esophageal squamous cell carcinoma (ESCC).MethodsPublished clinical trials in the PubMed, Medline, Embase databases on PD-1 inhibitors for the treatment of ESCC were searched, along with an additional search on abstracts from the American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) from inception to September 2021. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs) were synthesized using STATA.ResultsA total of 1970 patients (PD-1 inhibitors: 987; chemotherapy: 983) were enrolled in five randomized controlled trials. Compared with conventional chemotherapy, second-line PD-1 inhibitors significantly improved the OS (hazard ratio [HR] = 0.73, 95% confidence interval [CI]: 0.66–0.81; P < 0.001) and ORR (relative risk [RR] = 1.89, 95% CI: 1.16–3.05; P = 0.01) of advanced ESCC patients, especially significantly prolonged the OS in the patients with positive programmed death-ligand 1 (PD-L1) status (HR = 0.64, 95% CI: 0.53–0.77; P < 0.001); but did not better PFS (HR = 0.88, 95% CI: 0.68–1.14; P = 0.330) and DCR (RR = 0.89, 95% CI: 0.59–1.37; P = 0.603). Moreover, PD-1 inhibitors were associated with statistically lower incidences of grade 3–5 TRAEs.ConclusionSecond line PD-1 inhibitors significantly improved the OS and ORR of patients with advanced ESCC, especially the OS of those with positive PD-L1 expression, and did not result in significant improvement in PFS and DCR. Compared to chemotherapy, second-line PD-1 inhibitors had superior safety profiles for the treatment of advanced ESCC.
Highlights
Aim to establish the inhibitors of programmed cell death protein 1 (PD-1) as second-line therapy for advanced esophageal squamous cell carcinoma (ESCC)
Inclusion and exclusion criteria Studies eligible for the analyses satisfied each of the following requirements: srandomized controlled trials (RCT) on patients with advanced or metastatic ESCC refractory or intolerant to first-line therapy; trial participants in the PD-1 inhibitor arm received anti-PD-1 agent only, while participants in the chemotherapy arm were treated with conventional chemotherapy regimen; and the trial used at least three of the following (OS, progression-free survival [PFS], objective response rate [ORR], disease control rate [DCR], treatment-related adverse events [streatment-related adverse events (TRAE)] or grade 3–5 TRAEs) as outcome indicators
Extraction of data and assessment of risk of bias Data were extracted into a standardized form for data collection, which recorded the overall survival (OS) and PFS, ORR, DCR, TRAEs, grade 3–5 TRAEs in each eligible study and supplementary materials, and the clinicopathological information for each study, which included the first author of the publication, the year of publication, the name of the trial, the phase of the trial, treatment line, some patients, expression status of programmed death-ligand 1 (PD-L1), age, number of male patients, intervention and treatment, median follow-up
Summary
Aim to establish the inhibitors of programmed cell death protein 1 (PD-1) as second-line therapy for advanced esophageal squamous cell carcinoma (ESCC). Fluoropyrimidine/platinum-based systemic chemotherapy remains the first-line therapeutic option for patients with advanced or metastatic ESCC, severe toxicities from systemic chemotherapy limit its widespread application in clinical practice. In the past several years, multiple large randomized phase III trials on various targeted treatments in EC have been published, but no promising targeted therapy drug has been identified that can improve long-term outcomes of patients with advanced ESCC [4,5,6,7]. There are only a few treatment options for patients with unresectable or metastatic ESCC who progress on or are intolerant to first-line standard chemotherapy [4, 8, 9]. Because the positive expression rate of PD-L1 in ESCC reaches about 40% [10], PD-1 inhibitors are the most effective treatment candidates for EC
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