Clinical benefits of PD-1 inhibitors in specific subgroups of patients with advanced esophageal squamous cell carcinoma: a systematic review and meta-analysis of phase 3 randomized clinical trials

Abstract

PurposeIn recent years, a number of clinical trials have shown that programmed death 1 (PD-1) inhibitors offer significant survival benefits in patients with esophageal squamous cell carcinoma (ESCC). We conducted a meta-analysis to explore the antitumour efficacy of PD-1 inhibitor-based therapy in specific subgroups of patient with advanced ESCC.MethodsWe searched for eligible studies from the PubMed, Embase, Web of Science, Cochrane Library databases and conference abstracts. The indicators related to survival outcomes were extracted. The pooled hazard ratios (HRs) for overall survival (OS), progression-free survival (PFS) and duration of response (DOR) and the pooled odds ratio (OR) for objective response rate (ORR) were calculated to evaluate the efficacy of PD-1 inhibitor-based therapy in ESCC. Data regarding treatment lines, treatment regimens, programmed death ligand 1 (PD-L1) status, baseline demographic and disease characteristics were extracted. Subgroup analyses were conducted in specific populations of ESCC patients. The Cochrane risk of bias tool and sensitivity analysis were used to assess the quality of the meta-analysis.ResultsEleven phase 3 randomized controlled trials (RCTs) involving 6267 patients with ESCC were included in this meta-analysis. Compared with standard chemotherapy, PD-1 inhibitor-based therapy provided benefits in terms of OS, PFS, ORR, and DOR in all populations, the first-line treatment group, the second-line treatment group, the immunotherapy group, and the immunochemotherapy group. Although a limited PFS benefit was observed in second-line treatments and immunotherapy alone, PD-1 inhibitor-based therapy still reduced the risk of disease progression or death. Patients with high PD-L1 expression had a better OS benefit than those with low PD-L1 expression. The HR for OS favoured PD-1 inhibitor-based therapy over standard chemotherapy for all prespecified clinical subgroups.ConclusionsCompared with standard chemotherapy, PD-1 inhibitor-based therapy exhibited clinically meaningful benefits in patients with ESCC. Survival benefits were better in patients with high PD-L1 expression than in those with low PD-L1 expression, suggesting that the PD-L1 expression level can be used as a predictor of survival benefit from PD-1 inhibitor therapy. PD-1 inhibitor-based therapy provided a consistent benefit in reducing the risk of death according to prespecified subgroup analyses of clinical characteristics.

Tumor niche network-defined subtypes predict immunotherapy response of esophageal squamous cell cancer

“…This hypothesis was primarily supported by the growing evidence of the favorable outcomes observed in patients with elevated expression levels of immune checkpoint molecules following ICI therapy. 37 , 38 Furthermore, our analysis of reference immune cell datasets, specifically PBMC-R and PBMC-NR, indeed displayed higher expression of exhausted T cell markers.…”

ΔNp63-restricted viral mimicry response impedes cancer cell viability and remodels tumor microenvironment in esophageal squamous cell carcinoma

“…Another milestone multi-omics study subtyping lung SCC identified a "classical" subtype featuring amplification and expression of TP63/ΔNp63 along with downregulation of immune signaling (59). Immunotherapy has been increasingly explored and utilized in ESCC and lung SCC management (68,69). Identifying patients responsive to immunotherapy is crucial.…”

Cost-effectiveness analysis of tislelizumab plus chemotherapy as the first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma in China

“…The disease burden of oesophageal cancer is particularly significant in China [1,4], the disability-adjusted life years (DALYs) caused by oesophageal cancer ranks fourth among all cancers [5]. Advanced OSCC has a poor prognosis, with a 5-year survival rate of approximately 15-25% [6]. The efficacy of conventional chemotherapy regimens for advanced OSCC is limited, with less than one year of overall survival for patients treated with first-line cisplatin in combination with paclitaxel or fluorouracil regimens [6][7][8].…”