Targeted therapy and immunotherapy for gastric cancer: Biomarker-driven care

For now, gastric cancer is a group of diseases and thus is being treated as such. Thus, for some patients with gastric cancer, information about biomarkers is taken into account in addition to the conventional treatment using surgery, chemotherapy and radiation. The goal is to select the most appropriate targeted therapy or immunotherapy for individual patients. Biomarker-driven care utilizes a multitude of information regarding a patient’s tumor and the cancer as a whole to determine the most appropriate course of action for a patient’s specific case. Thus, while patients with similar clinical scenarios may receive similar treatment, in reality, each patient will likely receive unique treatment in light of their individual biomarker results and clinical scenario. What are biomarkers? Biomarkers can be almost anything that can be measured in relation to a tumor. This can be the amount of a protein in a cancer cell, a measure of the number of cell divisions in a tumor, the amount of substances in the blood or urine of a patient with cancer. In advanced gastric cancer biomarkers can be used to make decisions about treatment. For advanced gastric cancer, several biomarkers are of clinical relevance: HER2, PD-L1, mismatch repair (MMR) genes and corresponding levels of microsatellite instability (MSI), and CLDN18.2. Assessing for biomarkers such as HER2, PD-L1, mismatch repair or microsatellite instability status and CLDN18.2 using tumor tissue from a patient’s biopsy or from the resected tumor helps to identify the most appropriate treatment for individual patients. The results from biomarker testing, in conjunction with a patient’s clinical history and current status, provide additional information that may be considered during treatment planning. While the results of biomarker testing can give us an indication of the chances of successful treatment with certain types of therapies, there is no guarantee of efficacy. However, the test results do give us more information on the possible treatment options for you. Why biomarker testing matters Decisions about the treatment of gastric cancer are based on the stage and location of the primary tumor as well as the extent of spread to neighboring tissues or lymph nodes. In addition, consideration is given to the extent to which all cancer can be removed by surgery and the patient’s previous treatment for cancer. Finally, organ function and the patient’s overall health, including nutritional status, are taken into account. In cancer treatment, results of biomarker tests for tumors in a cancer patient are essential to decide on the individualized treatment approach for example, the test results can indicate whether a certain type of cancer can be treated with a targeted therapy or with immunotherapy. When deciding on the best treatment for a gastric cancer patient and discussing its benefits and risks, the appropriate treatment option for that patient must be chosen. Understanding HER2 The HER2 protein in gastric cancer is expressed at higher levels than average in a subset of gastric cancers and gastroesophageal junction cancers. Patients can be tested for the expression of the HER2 protein in their tumor and if positive, may be considered for HER2-directed therapies, depending on the overall clinical context. The monoclonal antibody trastuzumab is an example of HER2-directed treatment for gastric or gastroesophageal junction cancer with HER2-positive tumors. Treatment of patients with HER2-positive gastric or gastroesophageal junction cancer is not solely determined by the presence of HER2 in the cancer cells of the patient’s tumor. Other factors that are taken into consideration include the stage of cancer, previous treatment of the patient and the overall health of the patient. Can I find out if my tumor has been tested for HER2? And if so, what does it mean for my treatment? The role of PD-L1 The PD-L1 biomarker for treatment of advanced gastric cancer with immunotherapy. There are established methods and scoring systems to measure the amount of PD-L1 on cancer cells. This information can be used to determine whether a patient with advanced or metastatic gastric cancer may benefit from treatment with an immune checkpoint inhibitor. Immunotherapy for Gastric Cancer uses a completely different strategy than chemotherapy. Instead of directly killing cancer cells, immunotherapy activates the body’s immune system and, in some cases, it even removes blocks to the immune system that are put in place by other proteins to prevent immune activity. Just because a patient has gastric cancer does not mean that they will benefit from immunotherapy, and they must weigh the potential benefits against the potential risks for their individual situation. MSI and mismatch repair Mismatch repair (MMR) and microsatellite instability (MSI) testing can also provide insight to the biology of gastric cancer. Some gastric cancers are classified as mismatch repair deficient or microsatellite instability high. These tumors may have different considerations in their treatment. Gastric cancers are classified into mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) types. These tumors may be associated with responses to immune checkpoint inhibitors in appropriate clinical settings. The role of mismatch repair testing and/or MSI testing in gastric cancer treatment is becoming increasingly recognized. This information, in conjunction with the tumor’s pathology, the disease’s stage, previous treatment and other clinical information, can assist in the identification of the most appropriate therapy for gastric cancer patients. CLDN18.2 and targeted treatment Targeted treatment options for Gastric Cancer-CLDN18.2 is a protein expressed on the surface of gastric cancer cells. Recently, treatment has been developed for patients with gastric cancer whose tumors express CLDN18.2. For unresectable, locally advanced or metastatic, HER2-negative, gastric or gastroesophageal junction adenocarcinoma that are CLDN18.2-positive, zolbetuximab, in combination with fluoropyrimidine and a platinum, is approved by the FDA for adult patients. Biomarkers are only one part of care In summary, although biomarker testing is becoming more important for the treatment of gastric cancer patients, a treatment plan must always take into account the entire clinical picture of a patient. In assessing the cancer, imaging can give information about the size of a tumor, the spread of a tumor and whether a tumor is growing. The pathology report from the previous surgery and other tests, as well as the patient’s symptoms and overall health, are used in making a treatment plan. Information regarding biomarker testing may help patients understand potential treatment options. Treatment can change over time Even the best chosen treatment for a patient can change over time as the cancer develops, or the patient’s health changes. Sometimes new information from an imaging study, for example, or changes in the patient’s symptoms can prompt the health care provider to consider other treatment options. Additional pathology and biomarker information may become relevant as the cancer develops. New information, including from additional pathology and biomarker testing, can lead to changes in the treatment of a patient with cancer. Cancer may progress and the patient’s health may deteriorate. As a result, the health care provider may consider other treatment options. There are many reasons for continued communication with your doctor during cancer treatment. The main reason is that as your cancer progresses and your circumstances change your treatment may change as well. Supporting overall wellbeing It is important for the overall well-being of the patient to be taken into consideration when planning their gastric cancer treatment, although the biomarker-driven care will focus on the specific characteristics of the tumor in question. However gastric cancer has been shown to affect appetite, nutrition, energy, activity, emotional well-being and the quality of life of a patient with the disease. Assessment of a patient’s nutrition requirements and where necessary the provision of support to ensure that the patient’s requirements are met can form part of the overall treatment and care of a patient with gastric cancer. Discussions with patients about the goals of their treatment need to outline the expected benefits and risks of treatment. A full explanation of the expected side effects of any proposed treatment, and their implications, will enable patients to make the best decisions regarding their medical care. Looking ahead Gastric cancer research into the numerous new biomarkers as well as into new targeted therapies, into immunotherapies, into antibody-drug conjugates and others is ongoing. Future approaches for gastric cancer will rely on current understanding of the tumor biology. Treatment of gastric cancer will more and more be biomarker-driven to select the best treatment for individual patients. Established treatment options like surgery, chemotherapy and radiation therapy as well as supportive care for patients with cancer will remain the cornerstone of gastric cancer treatment. In summary, gastric cancer will be treated based on a better understanding of the primary tumor as well as the individual patient’s circumstances. Thus, more and more aspects of cancer management will be based on biomarker testing, in order to help identify appropriate treatment approaches for individual patients.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. 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