Treating Advanced Gastric Cancer
- Receiving an advanced gastric cancer diagnosis is overwhelming, but treatments are available to improve quality of life and extend survival.
- Chemotherapy, often the first treatment, can shrink tumors, relieve symptoms, and extend survival.
- When tumors have specific mutations, chemotherapy is combined with targeted drugs, such as trastuzumab for HER2-positive tumors or zolbetuximab for CLDN18.2 positive tumors, or combined with immunotherapy such as pembrolizumab for PD-L1-positive cancers.
- Patients should ask their doctors about molecular testing as the results can help tailor treatment and improve outcomes.
- In certain cases, participating in a clinical trial may be the best option. These trials provide access to cutting-edge treatments and research, helping both patients and the medical community advance care for gastric cancer.
Dr. Nicholas Hornstein, a medical oncologist at Northwell Cancer Institute in Manhattan, tells SurvivorNet that treatment at the advanced stage is a “bit of a marathon” rather than a sprint.
Read MoreChemotherapy
Chemotherapy is often the first line of treatment for metastatic gastric adenocarcinoma. Most cases of advanced gastric cancer are adenocarcinomas, meaning they originate from the cells lining the stomach.Chemotherapy can help shrink tumors, relieve symptoms, and extend survival. Combination chemotherapy, which typically involves drugs like fluoropyrimidine and oxaliplatin, is more effective than single agents but may also come with more side effects.
“If the cancer is found in an advanced stage, so large that the surgeons can’t remove it or if it has spread to other organs, it’s considered a stage four,” Dr. Sofya Pintova, a gastrointestinal medical oncologist at Mount Sinai Hospital in New York City, tells SurvivorNet.
“In that case, the treatment that we start with is what we call systemic treatment. Systemic treatment means medicines that go all over the body, get into the blood, get into all the areas where the cancer may be, and usually that treatment is dependent on many of the detailed features of the tumor itself,” she adds.
For those with tumors that are positive for a protein called HER2, adding trastuzumab, an immunotherapy drug, to chemotherapy can improve outcomes. HER2 is a protein that promotes cancer growth, and trastuzumab helps block it.
Immunotherapy
The immune system uses its white blood cells to attack cells in the body that are abnormal or foreign. Cancerous cells have the ability to prevent the immune system from doing its job. The cancer produces certain proteins to protect the tumor from white blood cells. As a result, the body does not recognize the tumor as abnormal.
Immunotherapy drugs like nivolumab (Opdivo) or pembrolizumab (Keytruda) stop this from happening and ensure the white blood cells recognize the cancer cell properly and attack it. The cancer cells themselves are not necessarily difficult to fight. However, they continue to divide rapidly. So, immunotherapy drugs help a patient’s immune system control their cancer on its own before it can spread.
In gastric cancer, immunotherapy is typically used in patients with specific biomarkers like high microsatellite instability (MSI-H) or high PD-L1 expression.
According to NCCN guidelines, if metastatic gastric cancer is documented or suspected, it’s mandatory to perform HER2, PD-L1, and microsatellite testing (if not done previously) .
PD-L1 and PD-1 inhibitors: checkpoint inhibitors
PD-L1 is a protein found on cancer cells while PD-1 is a protein found on normal cells. When they bind to each other, the immune system fails to recognize the cancer cell and switches off its defense mechanism marking the cancer cell as a normal cell. Between 55% and 65% of people with advanced gastric cancer have this protein.
Antibodies that target PD-L1 on cancer cells play a critical role in preventing the binding between normal and cancer cells (PD-L1 and PD-1) which activates the immune system (specifically T-cells) to recognize the cancer cell and stimulate an immune response.
What are checkpoint inhibitors?
Simply put, checkpoint inhibitors are a class of immunotherapy drugs that specifically target proteins found either on immune or cancer cells to prevent their binding together.
The advent of checkpoint inhibitors in treating cancer is that it doesn’t kill cancer cells directly, but it stimulates the immune system to find the cancer cells and attack them while hopefully not affecting other surrounding healthy cells.
Pembrolizumab (brand name Keytruda) or Nivolumab (brand name Opdivo) are examples of checkpoint inhibitors target PD-L1 on cancer cells.
HER2-Positive Advanced Gastric Cancer
HER2-positive refers to a characteristic found in certain cancer cells, where there’s an overexpression, or high level, of the HER2 protein.
This protein is a receptor on the surface of cells. When activated, the protein promotes cell growth.
In certain types of cancers, such as some advanced gastric cancer, this overexpression leads to the cancer cells growing and dividing much faster than normal cells, leading to disease that is far more aggressive compared to cancers that don’t express high levels of HER2.
The frequency of HER2 overexpression in gastric and gastroesophageal cancer ranges from 4.4% to 53%, with a mean of 18%
“Targeted drugs” like fam-trastuzumab deruxtecan (Enhertu) directly seek out and bind to HER2 proteins to effectively slow down or stop the growth of the cancer. Because it avoids harming healthy tissue surrounding the cancer, it can have fewer side effects compared to traditional chemotherapy. Patients with HER2-positive gastric cancer often benefit from other targeted drugs that specifically target HER2, like trastuzumab (Herceptin).
Dr. Anupama Nehra, the clinical director of hematology/oncology at the Rutgers Cancer Institute in New Jersey, explains why:
“It’s a bioengineered drug that essentially has more of an effect on the tumor cells compared to normal cells. So use of this medication actually helps minimize some of the effects on the normal tissue, but maximize the effects on the tumor tissues.”
Dr. Nehra adds that the drug delivers even more benefit thanks to a phenomenon called “the bystander effect.”
“This basically means that the surrounding tumor cells are also targeted by the medication,” she explains.
Patients with HER2-positive gastric cancer often benefit from other immunotherapy drugs that specifically target HER2, such as Herceptin.
Claudin 18.2 Testing
Make sure to ask your doctor about personalized treatment and molecular testing, which can look for specific characteristics in your cancer cells, like the expression of a protein called claudin 18.2. Testing for claudin 18.2 is a crucial step in determining whether a medication called Vyloy will be an effective treatment option. The drug has been approved for certain patients with locally advanced or metastatic gastric cancer.
The Importance of Clinical Trials
Taking part in a clinical trial may allow gastric cancer patients to access the most recent and cutting-edge treatments years before they’re approved by the Food and Drug Administration (FDA) and widely available, and these treatments can include immunotherapy, targeted therapy, gene therapy, or even a new combination of currently used treatments like surgery, chemotherapy, or radiation therapy.
“There is an incredible bevy of new therapies being developed. If I were a cancer patient with a widely spread metastatic cancer, I would want to be on a clinical trial,” Dr. Benjamin Neel, director of NYU Langone’s Perlmutter Cancer Center, told SurvivorNet in a previous conversation.
Although there’s no guarantee that a newly offered treatment will produce great results in curing cancer, at the very least, it can ensure proper care and follow-up from the healthcare team running the trial.
There’s also the knowledge that you’ll be helping doctors make ground-breaking discoveries and produce much-needed treatments.
Additionally, many of the fees or added costs that are directly related to the trial will be covered by insurance or the trial, so you will no longer have to pay to get treated.
Check out SurvivorNet’s simple Clinical Trial Finder tool here.
Questions to Ask Your Doctor
- What are my treatment options?
- Can you explain the benefits and side effects of the recommended treatments?
- What is my tumor’s PDL-1 level?/Is my tumor HER2-positive?
- What are the most common side effects of immunotherapy and how can I manage them?
- Are there any clinical trials or newer treatments available?
- What will insurance cover and what are my out of pocket costs?
Learn more about SurvivorNet's rigorous medical review process.
