Gastroesophageal Adenocarcinoma (GEA) is cancer of the stomach or the gastroesophageal junction. Management of GEA is determined by the stage of the cancer, the local tumor characteristics and the patient’s general health. Treatment for advanced or metastatic GEA has advanced considerably with the introduction of immunotherapy, allowing treatment approaches to be guided by specific biomarkers. As a result, a multidisciplinary approach is commonly used to support treatment planning for individual patients.
Understanding Disease and Diagnostic Evaluation
Patients with Gastroesophageal Adenocarcinoma typically present with difficulty swallowing, indigestion, upper abdominal pain, loss of appetite, weight loss and upper gastrointestinal hemorrhage. However, some of these symptoms are not specific to cancer and require further investigation as they persist or worsen.
Diagnostic evaluation for gastroesophageal cancer consists of an upper gastrointestinal endoscopy with biopsy to obtain a histopathological diagnosis of the tumor. Assessment of tumor extent is made with imaging studies, typically with computed tomography (CT) scans and, when indicated, with positron emission tomography (PET) scans. The endoscopic ultrasonography (EUS) can also provide information on the locoregional extent of the tumor.
Most important for the choice of systemic therapy is molecular profiling of the tumor. In clinical context this can include analysis of expression of programmed death-ligand 1 (PD-L1), assessment of mismatch repair (MMR) deficiency by testing for microsatellite instability (MSI). Other biomarkers which are of clinical relevance in specific situations can also be analyzed.
Treatment Approaches According to Disease Stage
Gastroesophageal adenocarcinoma treatment can be different depending on the extent of the tumor. Patients with tumors that can be removed by surgery are usually treated within a multimodal approach and, besides surgery, also receive perioperative (regarding the time of surgery) chemotherapy. Patients with inoperable tumor spreading within the esophagus, the stomach or adjacent organs or with distant metastasized cancer are primarily treated with systemic therapy.
There is often a need for treatment to be given as systemic therapy when tumors are deemed to be of an unresectable or metastatic nature. The choice of single agent or combination of chemotherapy and/or immunotherapy can be based on previous treatment(s), the presence of specific tumor biomarkers and their associated levels, and the potential treatment outcomes and tolerability for individual patients.
A structured approach to gastroesophageal adenocarcinoma treatment requires input from health care professionals from a variety of disciplines. Cases are discussed by different specialists, including the patient’s gastroenterologist, oncologist, surgeon, radiologist and pathologist, as well as health care professionals from different specialties, including specialist nurses.
Tislelizumab and Its Role in Immunotherapy
Tislelizumab is a PD-1 inhibitor, which inhibits the interaction of PD-1 and its ligands, and therefore prevents immune suppression by this pathway. Tislelizumab is designed to support antitumor immune activity through PD-1 pathway blockade; however, clinical benefit is not guaranteed in all patients.
Tislelizumab is known by the brand name Tevimbra. The role of tislelizumab in the management of gastroesophageal adenocarcinoma is described in the approved prescribing information, including the disease settings in which it has been evaluated in clinical studies, such as in combination with chemotherapy for certain patients with advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. Specific information in relation to use should be retrieved from the relevant Product Information in the treating clinician’s country in conjunction with local clinical guidelines.
In terms of clinical context, prior therapies, performance status, co-morbidities and contraindications all need to be considered prior to the use of tislelizumab. The use of tislelizumab may be influenced by the level of PD-L1 expression in the tumor and a number of other factors and biomarkers. However, these must be assessed using the specific assay and according to the specific criteria defined for that treatment in clinical trials.
Immunotherapy may be a treatment option for some patients with gastroesophageal adenocarcinoma. However, response to treatment with immunotherapy is variable. Individual patients have different circumstances and therefore need to be informed about the potential benefits, limitations, and uncertainties associated with treatment options, as well as the results of clinical trials that have investigated the treatment under consideration.
Safety Monitoring and Management of Adverse Events
In addition to the tumor, normal organs can be affected by immune activation, causing adverse events such as pneumonitis, colitis, hepatitis, endocrinopathy (e.g. hypothyroidism, hyperthyroidism), nephritis and others. Some immune-related adverse events may occur after the end of treatment.
Clinical practice typically includes a review and documentation of the patient’s medical history before starting immune-modulating therapy. In addition, baseline assessments of organ function should be conducted, and a monitoring plan should be established for potential immune-mediated adverse events.
In the context of gastroesophageal adenocarcinoma treatment with immunotherapy, monitoring for specific toxicities and other chemotherapy-related adverse effects, as well as the patients’ nutritional status, fluid status, pain and overall functional status, is essential.
Individualized Care and Ongoing Assessment
Ongoing assessment of gastroesophageal adenocarcinoma and its treatment is important to evaluate whether the treatment provides potential clinical outcomes and is being tolerated. Assessment can be based on clinical evaluation, imaging, laboratory tests and patients’ reports of symptoms and other effects on their lives.
Effective treatment of gastroesophageal cancer also includes aspects of supportive and/or palliative care. For patients with gastroesophageal cancer, nutritional interventions, symptom management and psychosocial support are important in addition to treatment and discussion of patients’ treatment preferences.
Conclusion
Gastroesophageal adenocarcinoma management requires accurate staging, individualized treatment planning, appropriate biomarker testing and evidence-based treatment options. Tislelizumab is an immunotherapy option in specific clinical settings, as outlined in its approved indications and supported by clinical evidence and precautions for its use. An individualized approach with active monitoring for toxicity and regular reassessment of treatment goals is important in the management of gastroesophageal adenocarcinoma.
Disclaimer: The information provided in this article is intended for educational purposes only and should not be interpreted as medical advice, a clinical guideline, or a recommendation for any specific treatment.
