What is the role of immunotherapy in gastric (stomach) cancer?

From the Guidelines

Immunotherapy is a crucial component in the treatment of gastric cancer, particularly for advanced or metastatic disease, with nivolumab being recommended for advanced, untreated gastric cancer with a PD-L1 CPS score ≥5. The use of immunotherapy in gastric cancer has been supported by recent studies, including the ESMO clinical practice guideline for diagnosis, treatment, and follow-up of gastric cancer 1. This guideline recommends the use of nivolumab with chemotherapy for advanced, untreated gastric cancer with a PD-L1 CPS score ≥5.

Key Points

• Immunotherapy, specifically immune checkpoint inhibitors like nivolumab, has shown benefit in the treatment of advanced or metastatic gastric cancer.
• Patient selection is crucial, with better responses seen in tumors with high PD-L1 expression.
• Combination approaches pairing immunotherapy with chemotherapy or targeted agents are being explored in clinical trials.
• The ESMO guideline recommends the use of nivolumab with chemotherapy for advanced, untreated gastric cancer with a PD-L1 CPS score ≥5 1.
• The ASCO guideline also supports the use of immunotherapy in the first-line treatment of advanced gastroesophageal cancer, with a focus on PD-L1 expression and HER2 status 1.

Treatment Approach

The treatment approach for gastric cancer should be individualized, taking into account the patient's PD-L1 status, HER2 status, and other clinical factors. Nivolumab with chemotherapy is a recommended first-line treatment option for advanced, untreated gastric cancer with a PD-L1 CPS score ≥5. The use of immunotherapy in combination with chemotherapy or targeted agents may become a standard first-line option in the future, as clinical trials continue to show promising results.

Side Effects and Monitoring

Immunotherapy can be associated with significant side effects, including fatigue, rash, diarrhea, and potentially serious immune-related adverse events. Close monitoring and management of side effects are crucial to ensure the safe and effective use of immunotherapy in gastric cancer treatment. Patients should be educated on the potential side effects and the importance of reporting any symptoms to their healthcare provider.

Future Directions

The use of immunotherapy in gastric cancer is a rapidly evolving field, with ongoing clinical trials exploring new combination approaches and biomarkers for patient selection. As new evidence emerges, treatment guidelines and recommendations may change, and healthcare providers should stay up-to-date with the latest developments to provide optimal care for their patients.

From the FDA Drug Label

Gastric Cancer in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test. in combination with fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.

The role of immunotherapy in gastric (stomach) cancer is as a first-line treatment in combination with chemotherapy for adults with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. This includes:

• HER2-positive gastric or gastroesophageal junction adenocarcinoma in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy.
• HER2-negative gastric or gastroesophageal junction adenocarcinoma in combination with fluoropyrimidine- and platinum-containing chemotherapy. 2

From the Research

Role of Immunotherapy in Gastric Cancer

• Immunotherapy has emerged as a promising approach for the treatment of gastric cancer, with various studies demonstrating its efficacy and tolerable toxicity compared to traditional therapies 3, 4.
• The development of immunotherapy for gastric cancer has been promoted by advances in understanding the microenvironment of cancer, and it can induce immune responses in patients, leading to the destruction of cancer cells 3.
• Different types of immunotherapies have been explored for gastric cancer, including immune checkpoint inhibitors, adoptive cell therapy, VEGF inhibitors, cancer vaccines, and CAR-T cell therapy 3, 4, 5.

Types of Immunotherapy

• Immune checkpoint inhibitors, such as pembrolizumab, have shown meaningful activity in gastric cancer and are being studied as upfront therapy in combination with chemotherapy 5.
• Adoptive cell therapies, cancer vaccines, and gene therapies have also been used with some initial successes in gastric cancer, although the results have been disappointing due to the inability to stimulate immunity efficiently 4.
• Monoclonal antibody therapies have been used to block negative regulators on the surface of T cells, limiting activation and proliferation of cytotoxic T cells, and have shown promise in overcoming immunosuppression 4.

Current Status and Future Directions

• Immunotherapy has become an important factor in the treatment of gastric cancer, with ongoing clinical trials exploring its efficacy in various settings 6.
• The selection of first-line immunotherapy regimens is crucial, and biomarkers such as PD-L1 expression are being used to guide treatment decisions 7.
• Novel biomarkers and therapeutic strategies are being assessed to refine the current treatment paradigm and improve outcomes for patients with gastric cancer 7.