HealthcareHER2-Positive Gastric Cancer Treatment: A Clear and Accessible Patient Guide

HER2-positive gastric cancer is a form of stomach cancer. Cancer cells in people with HER2-positive gastric cancer have higher levels of a protein called human epidermal growth factor receptor 2 (HER2). This protein is involved in the normal growth and development of cells but in cancer cells, it can help them to grow and divide more quickly. In some cases, there is also an increase in the number of HER2 genes in cancer cells, meaning that there is more HER2 protein produced.

Knowing the HER2 status of a patient’s tumor helps determine what kind of treatment he or she needs. Several treatment and diagnostic options are available, and selection depends on individual patient and disease characteristics. However, it is crucial to weigh up the potential benefits of treatment against the possible risks. In addition to the general state of an patient’s health and their potential of coping with the side effects, the cancer’s stage of development, its form and any previous treatment the patient has received all need to be considered.

What Makes Gastric Cancer HER2-Positive?

This type of gastric cancer is detected by HER2 testing. For patients with advanced or metastatic disease, knowing the HER2 status of their tumor can lead to the use of targeted therapies for their cancer.

Immunohistochemistry (IHC) assesses the amount of the HER2 protein in cancer cells and In Situ Hybridization (ISH) determines if there is an overexpression of the HER2 gene. In gastric cancer, the results from IHC testing can be measured by scores, and when necessary, by confirmatory ISH testing to determine the HER2 status of a tumor.

Measurement of tumor markers besides HER2, like PD-L1, MMR/MSI etc., is of importance to decide on the application of targeted treatments or even immunotherapies in gastric cancer. In accordance with current guidelines or in cases of clinical uncertainty and lacking better options the decision for apply such her2-positive gastric cancer treatment approaches has to be based on individual circumstances of the patient.

Treatment Options for HER2-Positive Gastric Cancer

If gastric cancer is localized, locally advanced or metastatic, then treatment would be directed by a multi-disciplinary team of medical oncologists, surgeons, radiation oncologists and radiologists etc.

Chemotherapy and HER2-Targeted Therapy

In cases of unresectable or metastatic cancer (in the stomach or the gastroesophageal junction), cancer patients are treated with a combination of chemotherapy and a targeted treatment for HER2-positive cancer. The most used targeted treatment for HER2-positive gastric cancer is Tislelizumab, which is directed against the HER2 protein. The HER2 protein is a growth-promoting substance on the surface of cancer cells. Tislelizumab blocks the signal of the HER2 protein, which leads to the death of cancer cells.

Medicines that are used to treat gastric cancer by killing cancer cells or by preventing cancer cells from dividing are used in combination with the HER2-targeted therapy. The chemotherapy for gastric cancer is generally a combination of a fluoropyrimidine (such as S-1, UFT, Tegafur, Capecitabine) and a platinum-based drug (such as cisplatin, Carboplatin).

The choice of anti-cancer medicines depends on various factors including the patient’s renal function, heart condition and presence of other medical conditions. It also depends upon previous treatment and the patient’s potential to tolerate side effects of anti-cancer medicines.

Immunotherapy in Selected Patients

Immuno-therapy aims to enhance the body’s own immune system to recognize and fight cancer cells. For patients with advanced HER2-positive gastric cancer, in selected cases, the treatment with pembrolizumab in combination with trastuzumab and chemotherapy might be an option according to the tumor characteristics and corresponding treatment guidelines or approval status.

The evaluation of PD-L1 expressions can support the use of immunotherapy. However, since, as with any cancer therapy, potential benefits have to be balanced by potential damage, treatment with immunotherapy may also lead to so-called immune related inflammation of for example the lungs, liver, thyroid or intestines.

Newer Targeted Treatments

Patients seeking information about her2 positive stomach cancer treatment should understand that treatment options may change when cancer progresses despite previous therapy. There is an antibody drug conjugate (ADC) called trastuzumab deruxtecan (also known as T-DXd) that links a cancer-killing drug to trastuzumab (a HER2-targeted therapy) which is specifically targeted to cells that express the HER2 protein.

Interstitial Lung Disease / Pneumonitis: Trastuzumab deruxtecan can cause serious lung inflammation, including Interstitial Lung Disease or Pneumonitis. Patients must report to their doctor immediately any signs or symptoms of lung inflammation such as new cough, shortness of breath, or fever while on treatment with this drug.

There are many more approaches to treat HER2-positive cancer including new antibody-drug conjugates, new HER2-targeted therapies to be used in combination, and therapies to overcome resistance to HER2-targeted therapy. These therapies are often investigated in clinical trials and patients with HER2-positive gastric cancer can be treated within a clinical trial if appropriate.

How Cancer Stage Influences Treatment

For local gastric cancer that can be removed by surgery and has not yet spread to other parts of the body, treatment may include surgery and sometimes chemotherapy before and/or after the surgery, depending on the location and extent of the cancer as well as the patient’s general state of health.

In advanced or metastatic gastric cancer, the goal of treatment is to stop the growth of cancer, to alleviate symptoms, to prolong life in patients with advanced cancer and to optimize their quality of life by using systemic treatment such as chemo-, target- or immunotherapy.

Regular assessment of the development of cancer and of treatment related side effects, for instance by clinical examination, by imaging studies and by analysis of blood samples, and assessment of symptoms, is part of the oncological treatment policy. In case of progression of cancer or in case of intractable side effects a change of the treatment policy is considered.

Managing Side Effects During Treatment

Side effects can vary from patient to patient as well as from one treatment to another. For example, chemotherapy often causes nausea or vomiting or tiredness or loss of appetite and diarrhea or mouth ulcers or reduced counts of blood cells. For example, trastuzumab may cause a decrease in left ventricular function.

Immunotherapy can cause the body to have an inflammatory reaction which can sometimes need to be treated urgently by a doctor. Trastuzumab deruxtecan has been associated with cases of respiratory symptoms which require monitoring by doctors.

Nutrition support, fluids and other measures to manage cancer treatment side effects need to be communicated to patients and families and patients reminded to take all their medicines as directed and report any new or worsening symptoms to their oncology team. A dietitian, symptom management clinician and psychosocial oncology support worker can also support patients on treatment.

Questions to Discuss with Your Oncology Team

Can I ask the following questions regarding my cancer and the recommended treatment for it:

• Does my tumor need to be tested for HER2 and what does the result of the test mean?
• Should the cancer be tested for other biomarkers, such as PD-L1, MSI/MMR?
• What are the goals of my recommended treatment?
• Which benefits and side effects should I expect?
• Are there any clinical trials, as well as other treatments, that would be suitable for me?

By having the right information about treatment options and by discussing all choices with your doctor you can make the choice that is in your best interest.

Looking Ahead

Research is ongoing to evaluate additional treatment approaches for HER2-positive gastric cancer. In addition to targeted treatments such as those currently used, immunotherapy and new combination treatments are also being investigated for use in appropriate cases.

Individuals with her2 positive stomach cancer should seek information about their specific situation including their pathology results, the stage of the cancer, past treatment(s) and overall health. The individualized treatment of gastric cancer patients includes their treatment as well as their monitoring for and management of side effects and symptoms.

Medical Disclaimer

This content is intended for general educational and informational purposes only and should not be considered medical advice, a diagnosis, or a substitute for consultation with a qualified healthcare professional. Localized gastric cancer and metastatic gastric cancer require different treatment approaches, and treatment decisions depend on the cancer stage, HER2 status, other relevant biomarkers, the patient’s overall health, and applicable clinical guidelines. Always consult a qualified oncologist to discuss diagnosis, treatment options, potential benefits, risks, and side effects before making any treatment decisions. Do not start, stop, or change prescribed treatment without medical guidance.