Zolbetuximab plus chemotherapy for locally advanced unresectable or metastatic stomach or gastroesophageal junction cancers: a plain language summary.

What Is This Summary About?: This is a summary of two articles. The first article is about a clinical trial called SPOTLIGHT and it was published in the medical journal in in April of 2023. The second article is about a clinical trial called GLOW and it was published in the medical journal in July of 2023.

Gastroesophageal Adenocarcinomas With Defective Mismatch Repair: Current Knowledge and Clinical Management.

Esophageal, gastroesophageal junction, and gastric adenocarcinomas, referred to collectively as gastroesophageal adenocarcinomas (GEAs), are a major cause of global cancer-related mortality. Our increasing molecular understanding has led to the addition of biomarker-directed approaches to defined subgroups and has improved survival in selected patients, such as those with HER2 and Claudin18.2 overexpression.

How to use anti-PD-1 therapy in gastric cancer: the approach in the United States.

Gastric cancer is a leading global cause of cancer-related mortality. In the past, survival achieved in metastatic disease with chemotherapy was less than 1 year. The advent of immune checkpoint inhibitors has changed the treatment of gastric cancer.

Neoplasia risk in patients with Lynch syndrome treated with immune checkpoint blockade.

Metastatic and localized mismatch repair-deficient (dMMR) tumors are exquisitely sensitive to immune checkpoint blockade (ICB). The ability of ICB to prevent dMMR malignant or pre-malignant neoplasia development in patients with Lynch syndrome (LS) is unknown. Of 172 cancer-affected patients with LS who had received ≥1 ICB cycles, 21 (12%) developed subsequent malignancies after ICB exposure, 91% (29/32) of which were dMMR, with median time to development of 21 months (interquartile range, 6-38).

Clinical and molecular characteristics of early-onset vs average-onset esophagogastric cancer.

Background: The rate of esophagogastric cancer is rising among individuals under 50 years of age. It remains unknown whether early-onset esophagogastric cancer represents a unique entity. This study investigated the clinical and molecular characteristics of early-onset and average-onset esophagogastric cancer .

Advances in the treatment of gastric cancer: 2022-2023.

Purpose Of Review: To review 2022-2023 studies in gastric cancer.

Recent Findings: Important studies report the role of laparoscopic surgery in gastric cancer, the activity of immune checkpoint inhibitors in metastatic, locally advanced and adjuvant therapy in gastric cancer, and the effectiveness of zolbetuximab in claudin 18.2-positive metastatic disease.

Prognostic value of circumferential radial margin involvement in esophagectomy for esophageal cancer: a case series.

Background: Residual tumor at the proximal or distal margin after esophagectomy is associated with worse survival outcomes; however, the significance of the circumferential resection margin (CRM) remains controversial. In this study, we sought to evaluate the prognostic significance of the CRM in patients with esophageal cancer undergoing resection.

Materials And Methods: We identified patients who underwent esophagectomy for pathologic T3 esophageal cancer from 2000 to 2019.

Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial.

There is an urgent need for first-line treatment options for patients with human epidermal growth factor receptor 2 (HER2)-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma. Claudin-18 isoform 2 (CLDN18.2) is expressed in normal gastric cells and maintained in malignant G/GEJ adenocarcinoma cells.

ILUSTRO: Phase II Multicohort Trial of Zolbetuximab in Patients with Advanced or Metastatic Claudin 18.2-Positive Gastric or Gastroesophageal Junction Adenocarcinoma.

Purpose: Zolbetuximab, an IgG1 monoclonal antibody, binds to claudin 18.2 (CLDN18.2) and mediates tumor cell death through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity.

Determinants of Survival with Combined HER2 and PD-1 Blockade in Metastatic Esophagogastric Cancer.

Purpose: We report updated clinical outcomes from a phase II study of pembrolizumab, trastuzumab, and chemotherapy (PTC) in metastatic esophagogastric cancer in conjunction with outcomes from an independent Memorial Sloan Kettering (MSK) cohort.

Patients And Methods: The significance of pretreatment 89Zr-trastuzumab PET, plasma circulating tumor DNA (ctDNA) dynamics, and tumor HER2 expression and whole exome sequencing was evaluated to identify prognostic biomarkers and mechanisms of resistance in patients treated on-protocol with PTC. Additional prognostic features were evaluated using a multivariable Cox regression model of trastuzumab-treated MSK patients (n = 226).

Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial.

Background: Zolbetuximab, a monoclonal antibody targeting claudin-18 isoform 2 (CLDN18.2), has shown efficacy in patients with CLDN18.2-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma.

Esophageal and Esophagogastric Junction Cancers, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.

Cancers originating in the esophagus or esophagogastric junction constitute a major global health problem. Esophageal cancers are histologically classified as squamous cell carcinoma (SCC) or adenocarcinoma, which differ in their etiology, pathology, tumor location, therapeutics, and prognosis. In contrast to esophageal adenocarcinoma, which usually affects the lower esophagus, esophageal SCC is more likely to localize at or higher than the tracheal bifurcation.

Durvalumab and PET-Directed Chemoradiation in Locally Advanced Esophageal Adenocarcinoma: A Phase Ib/II Study.

Objective: To determine the safety and efficacy of adding the anti-PD-L1 antibody durvalumab to induction FOLFOX and preoperative chemotherapy in locally advanced esophageal adenocarcinoma.

Background: Neoadjuvant induction FOLFOX followed by positron emission tomography (PET) directed chemoradiation has demonstrated improved survival for esophageal adenocarcinoma. There is clear benefit now for the addition of immune checkpoint inhibitors both in early and advanced stage disease.

Clinical Importance of Clonal Hematopoiesis in Metastatic Gastrointestinal Tract Cancers.

Importance: Clonal hematopoiesis (CH) has been associated with development of atherosclerosis and leukemia and worse survival among patients with cancer; however, the association with cancer therapy efficacy, in particular immune checkpoint blockade (ICB), and toxicity has not yet been established. Given the widespread use of ICB and the critical role hematopoietic stem cell-derived lymphocytes play in mediating antitumor responses, CH may be associated with therapeutic efficacy and hematologic toxicity.

Objective: To determine the association between CH and outcomes, hematologic toxicity, and therapeutic efficacy in patients with metastatic gastrointestinal tract cancers being treated with systemic therapy, both in the first-line metastatic treatment setting and in ICB.

Waiting to Operate: The Risk of Salvage Esophagectomy.

Objective: To assess postoperative morbidity, disease-free survival (DFS), and overall survival (OS) in patients treated with salvage esophagectomy (SE).

Background Data: A shift toward a "surgery as needed" approach for esophageal cancer has emerged, potentially resulting in delayed esophagectomy.

Methods: We identified patients with clinical stage I-III esophageal adenocarcinoma or squamous cell carcinoma who underwent chemoradiation followed by esophagectomy from 2001 to 2019.

Outcomes and Molecular Features of Brain Metastasis in Gastroesophageal Adenocarcinoma.

Importance: Brain metastasis (BrM) in gastroesophageal adenocarcinoma (GEA) is a rare and poorly understood phenomenon associated with poor prognosis.

Objectives: To examine the clinical and genomic features of patients with BrM from GEA and evaluate factors associated with survival.

Design, Setting, And Participants: In this single-institution retrospective cohort study, 68 patients with BrM from GEA diagnosed between January 1, 2008, and December 31, 2020, were identified via review of billing codes and imaging reports from the electronic medical record with follow-up through November 3, 2021.

Survival of Locally Advanced MSI-high Gastric Cancer Patients Treated With Perioperative Chemotherapy: A Retrospective Cohort Study.

Objective: To evaluate the efficacy of chemotherapy in patients with microsatellite instability (MSI)-high gastric cancer.

Background: Although MSI-high gastric cancer is associated with a superior prognosis, recent studies question the benefit of perioperative chemotherapy in this population.

Methods: Locally advanced gastric adenocarcinoma patients who either underwent surgery alone or also received neoadjuvant, perioperative, or adjuvant chemotherapy between 2000 and 2018 were eligible.