PD-1 inhibitors versus chemotherapy as second-line treatment for advanced esophageal squamous cell carcinoma: a meta-analysis

Abstract

Background Aim to establish the inhibitors of programmed cell death protein 1 (PD-1) as second-line therapy for advanced esophageal squamous cell carcinoma (ESCC). Methods Published 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. Results A 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. Conclusion Second 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.

Efficacy and Safety Profile of PD-1 Inhibitors Versus Chemotherapy in the Second-Line Treatment of Advanced Esophageal Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…In terms of clinical efficacy, our meta-analysis provided reliable evidence that PD-1 inhibitors could provide superior beneficial effects in OS and ORR in contrast to traditional chemotherapy in ESCC. The result was in concordance with the previous meta-analysis conducted in 2021 18,22 . Previous research has proved that tumor cells could upregulate PD-L1 expression to inhibit the function of T lymphocytes, thus evading persistent inflammatory or autoimmune reactions.…”

“…The result was in concordance with the previous meta-analysis conducted in 2021. 18,22 Previous research has proved that tumor cells could upregulate PD-L1 expression to inhibit the function of T lymphocytes, thus evading persistent inflammatory or autoimmune reactions. PD-1 inhibitors can block the binding of PD-L1 to PD-1, suppress the proliferation of PD-1 + cancer cells, interrupt the immune escape, and enable the T lymphocytes to eliminate cancer cells.…”

“…Pembrolizumab, Nivolumab, Camrelizumab, and other emerging PD-1 inhibitors have considerableclinical efficacy and safety advantages over traditional chemotherapy regimens, according to published results. In 2021, a meta-analysis examining the therapeutic efficacy and safety of PD-1 inhibitors revealed that second-line PD-1inhibitor drugs significantly increased the overall survival (OS) of patients with advanced ESCC 18 . However, not all of the included research was published in Extenso, and some valuable information was unavailable.…”

“…In 2021, a meta-analysis examining the therapeutic efficacy and safety of PD-1 inhibitors revealed that second-line PD-1inhibitor drugs significantly increased the overall survival (OS) of patients with advanced ESCC. 18 However, not all of the included research was published in Extenso, and some valuable information was unavailable. Now that these clinical trials have been published as a whole, we have the opportunity to reevaluate the clinical efficacy and safety with greater precision.…”

A Novel Predictor of Pathologic Complete Response for Neoadjuvant Immunochemotherapy in Resectable Locally Advanced Esophageal Squamous Cell Carcinoma

“…Multiple Phase III clinical studies have established the role of immunotherapy in the first-line or second-line treatment of advanced esophageal squamous cell carcinoma. 35 , 36 Immunotherapy combined with chemotherapy as neoadjuvant therapy has also been tried to be applied to locally advanced esophageal squamous cell carcinoma, in which efficacy and safety have also been observed. 16 , 37–39 PDL1 expression, tumor mutation load, microsatellite stability, and T cell function were reported to be correlated with the efficacy of immunotherapy.…”