Treatment for gastric cancer has continued to evolve over the last few years. While many patients are treated with chemotherapy as part of their systemic treatment, other treatments such as surgery and/or radiation, as well as targeted therapies and immunotherapy are used to treat gastric cancer. Therefore, gastric cancer treatment is not limited to chemotherapy and is given on an individual basis to each patient.
These are based on the location and stage of the cancer, whether the cancer can be removed by surgery, and the patient’s overall health. Biomarker testing results can also reveal the range of treatment options available to individual patients.
Understanding the Changing Treatment Landscape
Gastric cancer is not a single disease and thus can present in different forms. Different types of gastric cancer exist with different biological behaviors and thus require different treatment approaches.
Patients with potentially curable gastric cancer might be treated with an intent to cure. They can be treated for potentially curable gastric cancer by surgical resection of the tumor potentially preceded by and/or followed by chemotherapy and/or radiation therapy. Patients with locally advanced, unresectable, or metastasized disease are treated with the intent to control the disease and to alleviate symptoms. Patients with advanced disease are treated with systemic therapy.
In recent years, as several new gastric cancer treatments have been developed, deciding on the appropriate treatment is becoming increasingly complex. There are a number of factors to take into consideration, including the stage of the cancer, the nature of the primary tumor, the results of any biomarker testing, the patient’s general health, and treatment goals.
The Growing Role of Biomarker Testing
Biomarker testing for gastric cancer assesses the presence of various biomarkers such as HER2, PD-L1, MRE11, PMS2 and others in a tumor. This includes testing for the presence of the protein CLDN18.2 in a tumor of a gastric cancer patient. CLDN18.2 testing may help identify certain patients who could be eligible for an approved CLDN18.2-directed treatment.
HER2 expression can be used to determine if a patient with gastric cancer would benefit from a HER2 targeted therapy. In addition, PD-L1 expressions on tumor cells can help to determine if a patient may benefit from an immune checkpoint inhibitor. Mismatch repair deficient/microsatellite instability high gastric cancers are a distinct entity from non-MR/Msi gastric cancers.
There are many newly identified clinically relevant biomarkers. For instance, there is a newly identified clinically relevant biomarker CLDN18. Zolbetuximab (in combination with fluoropyrimidine- and platinum-containing chemotherapy) has been approved by the U.S. Food and Drug Administration for the treatment of certain adult patients with HER2-negative, CLDN18.2-positive, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Follow-up biomarker test results are important to select the right gastric cancer treatment for patients. Pathology testing for biomarkers can help identify the most appropriate treatment for individual patients.
Moving Beyond Chemotherapy
It remains true that for most patients with gastric cancer, a combination of chemotherapy, usually with a fluoropyrimidine as the backbone, and/or targeted therapy and/or immunotherapy, when appropriate, and in conjunction with supportive care, may be considered depending on various factors.
Immunotherapy is a type of cancer treatment that works differently from traditional chemotherapy. While chemotherapy typically kills cancer cells directly, immunotherapy uses the body’s immune system to help destroy cancer cells. Immune checkpoint inhibitors, for example, are a type of immunotherapy that works by helping the immune system recognize and attack cancer cells.
Pembrolizumab is used in certain FDA-approved gastric or gastroesophageal junction cancer treatment settings. Eligibility may depend on factors such as HER2 status, PD-L1 expression, disease setting, and the specific treatment regimen.
Gastric cancer treatment is rapidly evolving and thus chemotherapy is often given in conjunction with other therapeutic agents to obtain a desirable outcome for a given cancer type.
Targeted Treatment for Selected Patients
These therapies work by attacking specific targets. The targets are often molecules that in normal cells promote growth and development. Others are part of signal transduction pathways. As with other therapies, targeted therapies are given to patients with cancer whose tumors express the target of the therapy. Patients are also required to meet specific criteria.
For example, some HER2 positive gastric cancers express the HER2 protein in a manner that allows for treatment with HER2 targeted therapies, such as trastuzumab. More recently, gastric cancers expressing the protein CLDN18.2 have been found to be treated with zolbetuximab, in combination with fluoropyrimidine- and platinum-containing chemotherapy, for patients with advanced disease.
Some targeted therapies may continue until the disease progresses. Biomarker testing may help healthcare professionals identify gastric cancer treatment options that could be appropriate for an individual patient.
Considering Immunotherapy
Immunotherapy is used for advanced gastric cancer in selected patients, based on the level of expression of PD-L1 in cancer cells and other factors. Such treatment may be given after prior therapy and within the scope of approved treatments and treatment guidelines.
Immunotherapy may not benefit every gastric cancer patient, in some cases even lead to side effects. Deciding on or rejecting an immune checkpoint inhibitor is a case-by-case decision based on the individual patient’s situation and taking both potential benefits and possible side effects into account. The reasons for considering immunotherapy can be discussed with the healthcare team as part of treatment planning.
Treatment Decisions Can Change
When considering gastric cancer treatment for a patient, the treatment plan is not set in stone. New information might be found when doing an imaging test, reviewing a patient’s pathology, or doing biomarker testing. The patient’s overall health, how their cancer is growing, and their response to prior treatment can all play a role in deciding on a new treatment plan.
After having received prior treatment a change in treatment may be considered. Some cancers may even have an unexpected regression. Sometimes the side effects are even more than normal for a certain treatment. This treatment is given based on the amount of prior treatment the patient received, organ function, nutritional status as well as performance status. Other medical problems are also considered, and the physician would discuss benefits and risks of a certain treatment with the patient to decide the most appropriate mode of treatment. Treatments that may be appropriate for one patient may not be appropriate for other patients with the same diagnosis.
Supporting Quality of Life
Although many of the issues related to gastric cancer treatment affect the physical health of a patient, with influences on their appetite, nutrition, energy, physical function and emotions, their medical treatment is not the only issue to be considered.
Nutritional assessment is important for gastric cancer patients who cannot eat due to their cancer or are losing weight, often because of their cancer or its treatment. Supportive care to control symptoms and to deal with treatment side effects is also important. It is very important for the patient to discuss treatment goals with the physician, who can describe the expected benefits, risks and side effects of a certain treatment. The physician may also explain the potential impact of the treatment on daily life and help the patient to find the appropriate treatment.
Looking Toward the Future
Clinical trials are evaluating targeted therapies, antibody-drug conjugates and treatments that are based on immune modulation. Gastric cancer treatment is becoming increasingly individualized with each patient’s cancer being treated based on its individual characteristics. There is, however, a growing number of different approaches for the treatment of individual cases of gastric cancer. Therefore, the appropriate treatment for individual cases of gastric cancer is determined by discussion with doctors.
Medical Disclaimer: The information provided in this article is intended for educational purposes only and should not be interpreted as medical advice, clinical guidelines, or a recommendation for any specific treatment.