Current Status of Checkpoint Inhibitors in the Treatment of Esophageal and Gastric Tumors – Overview of Studies

Vrána, David; Matzenauer, Marcel; Melichar, Bohuslav

doi:10.14735/amko201835

Cited by 3 publications

(2 citation statements)

References 12 publications

(12 reference statements)

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“…Esophageal cancer are tumors with high mutation loads that have attracted considerable attention since the beginning of interest in ICIs. [ 20 ] In the clinical trial of KEYNOTE-028 and number ONO-4538-07/JapicCTI-No.142422, ICIs also showed promising antitumor activity and a manageable safety profile. [ 21 , 22 ] Phase II clinical study KEYNOTE-180 further confirmed the sustained efficacy and controllable adverse effects of Pembrolizumab in the third-line and above treatment of advanced esophageal cancer.…”

Section: Discussionmentioning

confidence: 99%

Refractory solitary cervical lymph node metastasis after esophageal squamous cell carcinoma surgery and its successful treatment with immune checkpoint inhibitor

Song¹,

Wang²,

Tian³

et al. 2020

Medicine

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Rationale: Although the early detection and treatment of non-metastatic esophageal cancer has improved, these patients’ prognoses are still poor. Most patients with radical treatment for esophageal cancer will relapse in 3 years, and the best treatment strategy after recurrence has not been uniformly accepted. Multiform treatments may be beneficial to recurrent patients. Patient concerns: A 60-year-old male patient, due to routinely health examination, ulcerated lesions 30 cm away from the incisors were found by gastroscopy, pathology showed esophageal squamous cell carcinoma (ESCC). Diagnosis: Due to the patient's pathology, he was diagnosed with ESCC. Interventions: The patient underwent radical surgery for ESCC on June 28, 2015. The left cervical lymph node metastasis occurred after 20 months, and lymph node metastasis carcinoma resection was performed. After that, concurrent chemoradiotherapy was implemented, 40 days after the end of the 4 courses of chemotherapy, the left cervical metastatic lymph nodes relapsed, radioactive particle implantation was carried out, and progressed again after 1 month. The patient took apatinib for 1 week but could not tolerate due to hand-foot syndrome. Immune checkpoint inhibitor (ICI) was administered since October 27, 2017. Outcomes: The therapeutic effect of immune checkpoint inhibitor was evaluated as partial response (PR) after 6 courses of treatment and complete response (CR) after 15 courses of treatment. To our knowledge, this is the first case report of successful immunotherapy for refractory esophageal squamous cell carcinoma. Lessons: The emergence of ICIs promotes the treatment of esophageal cancer to a new era. Our observations suggest that patients for whom schedule to receive anti-programmed cell death protein-1 (anti-PD-1)/programmed cell death-ligand 1 (PD-L1) immunotherapy may require genomic testing to predict whether tumors respond to ICIs. In this case, we also present the predictors for the efficacy of targeted immunotherapy. At present, no matter which predictor of PD-L1 expression, tumor mutational burden (TMB), microsatellite instability (MSI), and tumor-infiltrating lymphocyte (TIL), a single predictor may be unconvincing and cannot accurately estimate the efficacy of immunotherapy. Multiplex detecting methods and combined biomarkers may provide new strategies. Consensus need to be reached in order to be widely applied in future studies.

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Section: Discussionmentioning

confidence: 99%

Refractory solitary cervical lymph node metastasis after esophageal squamous cell carcinoma surgery and its successful treatment with immune checkpoint inhibitor

Song¹,

Wang²,

Tian³

et al. 2020

Medicine

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“…Pembrolizimab, Nivolumab) enhancing antitumor T-Cell activity through the inhibition of immune checkpoints, like the programmed death-1 (PD-1) receptor [9] and improved survival in some solid tumors like malignant melanoma and non-small cell lung carcinoma [10][11][12][13]. First line and second line treatment of metastatic esophageal cancer with checkpoint inhibitors considering the PD1/PDL1 axis are currently tested in a Phase III evaluation with pembrolizumab (KEY-NOTE-062, KEYNOTE-061) [14] as well as nivolumab (CheckMate-577) in the adjuvant setting with various other approaches in all lines of therapy [15].…”

Section: Introductionmentioning

confidence: 99%

Immune profile and immunosurveillance in treatment-naive and neoadjuvantly treated esophageal adenocarcinoma

Wagener‐Ryczek

Schoemmel

Kraemer

et al. 2020

Cancer Immunol Immunother

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The outcome in esophageal adenocarcinoma (EAC) is still poor with only 20% of patients in Western populations surviving for more than 5 years. Almost nothing is known about the precise composition of immune cells and their gene expression profiles in primary resected EACs and also nothing compared to neoadjuvant treated EACs. This study analyzes and compares immune profiles of primary resected and neoadjuvant treated esophageal adenocarcinoma and unravels possible targets for immunotherapy. We analyzed 47 EAC in total considering a set of 30 primary treatment-naive EACs and 17 neoadjuvant pretreated (12 × CROSS, 5 × FLOT) using the Nanostring's panel-based gene expression platform including 770 genes being important in malignant tumors and their immune micromileu. Most of the significantly altered genes are involved in the regulation of immune responses, T-and B cell functions as well as antigen processing. Chemokine-receptor axes like the CXCL9,-10,-11/CXCR3-are prominent in esophageal adenocarcinoma with a fold change of up to 9.5 promoting cancer cell proliferation and metastasis. ARG1, as a regulator of T-cell fate is sixfold down-regulated in untreated primary esophageal tumors. The influence of the currently used neoadjuvant treatment revealed a down-regulation of nearly all important checkpoint markers and inflammatory related genes in the local microenvironment. We found a higher expression of checkpoint markers like LAG3, TIM3, CTLA4 and CD276 in comparison to PD-L1/PD-1 supporting clinical trials analyzing the efficacy of a combination of different checkpoint inhibitors in EACs. We found an up-regulation of CD38 or LILRB1 as examples of additional immune escape mechanism. Keywords Esophageal adenocarcinoma • Immune profile • RNA expression • Nanostring Abbreviations ARG1 Arginase 1 CTA Cancer testis antigen CCR3 CC chemokine receptor type 3 CXCL9 Chemokine (C-X-C motif) ligand 9 CD Cluster of differentiation CROSS CROSS-trial regimen with paclitaxel, carboplatin and 41.4 Gy/23 fractions CSM Consensus molecular subtype CTLA-4 Cytotoxic T-lymphocyte-associated protein 4 DNAse Deoxyribonuclease EBV Epstein-Barr virus EAC Esophageal adenocarcinoma FC Fold change Svenja Wagener-Ryczek and Max Schoemmel contributed equally to this work.

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The Role of Immunotherapy in Esophageal and Gastric Cancer

Dedecker

Teuwen

Vandamme

et al. 2023

Clinical Colorectal Cancer

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Current Status of Checkpoint Inhibitors in the Treatment of Esophageal and Gastric Tumors – Overview of Studies

Cited by 3 publications

References 12 publications

Refractory solitary cervical lymph node metastasis after esophageal squamous cell carcinoma surgery and its successful treatment with immune checkpoint inhibitor

Refractory solitary cervical lymph node metastasis after esophageal squamous cell carcinoma surgery and its successful treatment with immune checkpoint inhibitor

Immune profile and immunosurveillance in treatment-naive and neoadjuvantly treated esophageal adenocarcinoma

The Role of Immunotherapy in Esophageal and Gastric Cancer

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