Dataset Information

PD-1 Inhibitors in the Advanced Esophageal Cancer.

ABSTRACT: Esophageal cancer (EC) is a lethal disease, and ranks 7th in incidence and 6th in mortality worldwide. Patients are treated with surgery and/or chemoradiotherapy for a curative intent, but for those with advanced diseases systemic chemotherapy and targeted therapy are the mainstay treatment with poor prognosis. For the patients with squamous cell carcinoma and those progressed after chemotherapy, treatment option is even fewer, and effective treatment modalities are urgently needed. Preclinical and clinical studies have found the PD-1/PD-L1 inhibitors activate T lymphocytes, inhibit cancer growth, and improve survival in cancer patients. Multiple PD-1/PD-L1 inhibitors have been approved for the management of a variety of cancers. Interestingly, a large of proportion of EC patients have tumors with PD-L1 expression and high tumor mutation burden. Trials have been performed to evaluate the efficacy and safety of the PD-1/PD-L1 inhibitors in EC patients. This review will summarize the current progress in this field, especially the toxicities associated with these agents.

SUBMITTER: Hong Y

PROVIDER: S-EPMC6916418 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

PD-1 Inhibitors in the Advanced Esophageal Cancer.

Hong Ye Y Ding Zhen-Yu ZY

Frontiers in pharmacology 20191129

Esophageal cancer (EC) is a lethal disease, and ranks 7th in incidence and 6th in mortality worldwide. Patients are treated with surgery and/or chemoradiotherapy for a curative intent, but for those with advanced diseases systemic chemotherapy and targeted therapy are the mainstay treatment with poor prognosis. For the patients with squamous cell carcinoma and those progressed after chemotherapy, treatment option is even fewer, and effective treatment modalities are urgently needed. Preclinical ...[more]

PMID: 31920637

Similar Datasets

Project description:Recently, a sum of trials of programmed cell death-1 (PD-1) inhibitors combined with chemotherapy have shown excellent efficacy compared to chemotherapy alone in patients with previously untreated, advanced esophageal squamous cell carcinoma (ESCC). However, there is no head-to-head comparison and consensus on which immunotherapy regimen results in better survival outcomes. This study aimed to evaluate the survival efficacy of various PD-1 inhibitor-based therapies in the first-line treatments for patients with advanced ESCC. Data collected prior to 31 July 2023 were searched in the PubMed, Cochrane Library, Embase, Medline, and Web of Science databases. Overall survival (OS) and progression-free survival curves were pooled using the MetaSurv package. Survival data were compared by reconstructed individual patient data. A total of 4,162 patients and seven randomized controlled trials were included. After synthesizing, PD-1 inhibitors prolonged median OS from 11.3 months (95% CI (confidence interval) 10.7-11.7) to 15.6 months (95% CI 14.7-16.3). Based on reconstructed patient-level data, the toripalimab, tislelizumab, and sintilimab group achieved the longest OS, whereas the sintilimab and tislelizumab group had the lowest risk of recurrence than other treatments. In patients with a combined positive score of ≥10, sintilimab had better OS efficacy than pembrolizumab (HR: 0.71, 95% CI: 0.52-0.96). In terms of tumor proportion score of ≥1%, camrelizumab, nivolumab, and toripalimab showed proximate survival benefits in both OS and progression-free survival. PD-1 inhibitor combined with chemotherapy significantly improved the survival time of patients with advanced ESCC. Toripalimab, tislelizumab, and sintilimab plus chemotherapy showed the best OS benefit. Longer progression-free benefits might be generated from adding tislelizumab and sintilimab to chemotherapy. Sintilimab was strongly recommended for patients with high programmed cell death-ligand 1 abundance. [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42024501086].

Project description:Preliminary clinical studies of anti-programmed cell death-1 (anti-PD-1) therapy in gastro-esophageal cancers have suggested promising single-agent activity. In patients who received prior treatment for advanced disease, pembrolizumab has been associated with a response rate of 20% in programmed cell death-1 ligand 1 (PD-L1)-positive tumors, and nivolumab with a response rate of 12% in unselected tumors. Both agents yielded a median duration of response lasting ~6-7 months. PD-L1 expression and microsatellite instability (MSI) have emerged as potential predictive markers for PD-1/PD-L1 blockade. PD-L1 expression in tumor cells and in immune cells within the tumor microenvironment has been detected in 14-24% and ~35% of patients with gastro-esophageal cancer, respectively. PD-L1 tumor cell expression appears to be more common in Epstein-Barr virus (EBV)-positive gastric cancers (GCs) and has been associated with an increased density of tumor-infiltrating lymphocytes (TIL). To date, data are too sparse to determine whether PD-L1 expression predicts efficacy of anti-PD-1 therapy in gastro-esophageal cancer, but data from other tumor types have not been consistent regarding its predictive value. MSI occurs in 10-20% of gastro-esophageal cancers and arises from deficient mismatch repair (MMR). MSI is highly correlated with non-synonymous mutation burden, as well as a dense accumulation of TILs. MSI has been associated with improved response to anti-PD-1 therapy in gastrointestinal cancers. Multiple studies are ongoing which examine therapeutic blockade of the PD-1/PD-L1 axis in unselected patients with gastro-esophageal cancer, as well as patients whose tumors express PD-L1 or exhibit MSI. These studies will clarify their activity in this disease and potentially can determine whether identify a strong predictive biomarker can be identified. Checkpoint inhibition is also being studied in combination with curative-intent chemo (radio) therapy and surgery.

Project description:Immune checkpoint inhibitors (ICIs) are recommended as first-line treatment for late-stage non-small cell lung cancer (NSCLC), either as monotherapy or in combination with chemotherapy. However, efficacy and safety comparisons between ICIs as monotherapy and ICIs with chemotherapy are lacking. We searched PubMed, Embase, and Cochrane Library for randomized controlled trials published before February 29th, 2020, with the search terms "immunotherapy" and "chemotherapy". 10 eligible trials were identified with a total of 5,956 patients. Of these patients, 3,204 received immune therapy and 2,752 received chemotherapy. PD-1 inhibitors with chemotherapy improved OS (HR 0.84, 0.77-0.92), PFS (HR 0.80, 0.75-0.85), and objective response rate (ORR) (odds ratio (OR) 2.55, 1.20-5.28) compared to PD-1 inhibitors as monotherapy. In contrast, PD-L1 inhibitors plus chemotherapy showed no significant differences in OS, PFS, or ORR compared with PD-L1 inhibitors as monotherapy. When patients were stratified according to PD-L1 expression level, patients with high PD-L1 expression (≥ 50%) receiving PD-1 inhibitors plus chemotherapy had improved PFS, but not other outcomes, compared to PD-1 inhibitors as monotherapy. In these patients, PD-L1 inhibitors plus chemotherapy showed no significant difference in survival compared with PD-L1 inhibitors. In the low PD-L1 expression group (1%-49%), PD-1 inhibitors plus chemotherapy improved OS and PFS, but no advantage was observed in PD-L1 inhibitors plus chemotherapy in OS, PFS, or ORR compared with PD-L1 inhibitor monotherapy. When comparing PD-1/PD-L1 inhibitors plus chemotherapy with PD-1/PD-L1 inhibitors monotherapy, no significant differences were observed in the rate of immune-related adverse events (AEs). In summary, for treating patients with late-stage NSCLC, PD-1 inhibitors plus chemotherapy have improved efficacy compared with PD-1 inhibitor monotherapy, but PD-L1 inhibitors plus chemotherapy have similar efficacy as PD-L1 monotherapy. Survival benefits of PD-1/PD-L1 inhibitors combined with chemotherapy were particularly significant in patients with low PD-L1 expression levels.Systematic review registrationPROSPERO, identifier CRD42020166678 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=166678).

Dataset Information

PD-1 Inhibitors in the Advanced Esophageal Cancer.

Publications

PD-1 Inhibitors in the Advanced Esophageal Cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets