Trial reportJournal for immunotherapy of cancer2021
Phase II study of pembrolizumab in refractory esophageal cancer with correlates of response and survival.
Trial report in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 28 citations in OpenAlex.
- Peripheral blood cytokines and outcomes with immune checkpoint blockade: a systematic review and meta-analysis.Immunotherapy · 2024Pooled it
- Peripheral cytokine levels as novel predictors of survival in cancer patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis.Frontiers in immunology · 2022Pooled it
- Harnessing biomarkers to guide immunotherapy in esophageal cancer: toward precision oncology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- SMARCA4-Deficient Carcinomas of the Small Intestine: A Systematic Review.Current oncology (Toronto, Ont.) · 2026Review
- Association between tumor volume changes during neoadjuvant chemoimmunotherapy and survival outcomes in esophageal squamous cell carcinoma: a multicenter study.Frontiers in immunology · 2026Article
- Unmasking immune checkpoint resistance in esophageal squamous cell carcinoma: Insights into the tumor microenvironment and biomarker landscape.World journal of gastrointestinal oncology · 2025Review
- A pilot study investigating the effect of pembrolizumab on the tumoral immunoprofile of newly diagnosed mullerian cancers.Gynecologic oncology reports · 2025Article
- Toxicity Associated with Pembrolizumab Monotherapy in Patients with Gastrointestinal Cancers: A Systematic Review of Clinical Trials.Biomedicines · 2025Review
- Research progress on mechanisms of tumor immune microenvironment and gastrointestinal resistance to immunotherapy: mini review.Frontiers in immunology · 2025Review
- Prognostic and predictive value of angiogenesis-associated serum proteins for immunotherapy in esophageal cancer.Journal for immunotherapy of cancer · 2024Article
- Prognostic biomarkers for immunotherapy in esophageal cancer.Frontiers in immunology · 2024Review
- Peptidoglycan induces CXCL10 production and inhibits esophageal squamous cell carcinoma proliferation.American journal of cancer research · 2024Article
- Efficacy of the induced pluripotent stem cell derived and engineered CD276-targeted CAR-NK cells against human esophageal squamous cell carcinoma.Frontiers in immunology · 2024Article
- Opportunities and challenges in combining immunotherapy and radiotherapy in esophageal cancer.Journal of cancer research and clinical oncology · 2023Review
- Diagnosis and management of gastrointestinal SMARCA4-deficient undifferentiated tumors.Clinical journal of gastroenterology · 2023Article
- Toosendanin targeting eEF2 impedes Topoisomerase I & II protein translation to suppress esophageal squamous cell carcinoma growth.Journal of experimental & clinical cancer research : CR · 2023Article
- Clinical and prognostic significance of perioperative change in red cell distribution width in patients with esophageal squamous cell carcinoma.BMC cancer · 2023Article
- Is the combination of immunotherapy with conventional chemotherapy the key to increase the efficacy of colorectal cancer treatment?World journal of gastrointestinal oncology · 2023Review
- T-cell exhaustion and stemness in antitumor immunity: Characteristics, mechanisms, and implications.Frontiers in immunology · 2023Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundImmune checkpoint inhibitors have revolutionized cancer treatment, but the benefits in refractory patients with esophageal cancer have been modest. Predictors of response as well as new targets for novel therapeutic combinations are needed. In this phase 2 clinical trial, we tested single-agent pembrolizumab in patients with advanced esophageal cancer, who received at least one prior line of therapy.
methodsPembrolizumab 200 mg every 3 weeks was tested in 49 patients with refractory esophageal cancer: 39 with adenocarcinoma and 10 with esophageal squamous cell carcinoma. Major endpoints were radiological response by Immune-related Response Evaluation Criteria In Solid Tumors and survival. Tumor samples were evaluated for programmed cell death ligand 1 (PD-L1) expression, tumor mutational burden (TMB), and immune contexture by both NanoString mRNA expression analysis and flow cytometry. Peripheral blood mononuclear cells and a panel of circulating chemokines were also analyzed.
resultsThe overall response rate (ORR) was 8% (4 of 49 patients; 95% CI 2.3% to 19.6%). Median overall survival (OS) was 5.8 months (95% CI 4.0 to 9.5). ORR and OS were not associated with histology. For PD-L1-positive patients, ORR was 13.3% (95% CI 1.7% to 40.5%) and median OS was 7.9 months (95% CI 4.7 to 15.5). A trend toward improved OS was observed in seven patients with a TMB ≥10 mut/Mb (p=0.086). Tumors with a PD-L1 Combined Positive Score ≥1 showed enrichment of LAG3 (p=0.005) and IDO1 (p=0.04) gene expression. Baseline levels of circulating CXCL10, interleukin 2 (IL2) receptor α (IL2RA) and IL6 were associated with survival: CXCL10 favorably, (HR 0.37, p=0.002 (progression-free survival); HR 0.55, p=0.018 (OS)); IL2RA and IL6 unfavorably (HR 1.57, p=0.020 for IL6 (OS); HR 2.36, p=0.025 for IL2RA (OS)).
conclusionsPembrolizumab monotherapy was modestly effective in refractory esophageal cancer. Circulating CXCL10 at baseline appeared to be a robust predictor of response. Other T cell exhaustion markers are upregulated in PD-L1-positive patients, suggesting that immunotherapy combinations such as anti-LAG3/programmed cell death protein 1 (PD-1) or anti-IDO1/PD-1 may be of promise in refractory esophageal cancer.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.