Treatment of Stage IV Gastric Cancer
Medically reviewed by Dr. C.H. Weaver M.D. Medical Editor 10/2018
Patients with stage IV gastric cancer have cancer that has spread to distant sites. Optimal treatment for some patients with stage IV gastric cancer often requires more than one therapeutic approach. Thus, it is important for patients to be treated at a medical center that can offer multi-modality treatment involving medical oncologists, radiation oncologists, surgeons, gastroenterologists and nutritionists.
For patients with Stage IV gastric cancer, surgery may be performed in order to reduce bleeding or to keep the cancer from obstructing the intestines or stomach.
Chemotherapy can relieve symptoms and extend survival among patients with advanced gastric cancer. Several chemotherapy regimens are available, and the choice of which to use depends in part on the patient’s health. Chemotherapy may be used in combination with other treatments such as precision cancer medicine, radiation therapy, and/or surgery.
Precision Cancer Medicine
The purpose of precision cancer medicine is not to categorize or classify cancers solely by site of origin, but to define the genomic alterations in the cancers DNA that are driving that specific cancer. Precision cancer medicine utilizes molecular diagnostic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Once a genetic abnormality is identified, a specific targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack gastric cancer cells with specific abnormalities, leaving normal cells largely unharmed.
Herceptin® (trastuzumab) is a targeted therapy that interfere with specific pathways involved in the growth or spread of cancer. A protein known as HER2 (human epidermal growth factor receptor contributes to cancer growth and cancers that test positive for HER2 may be treated with a HER2-targeting drug called Herceptin® (trastuzumab). Herceptin is often used in combination with chemotherapy, and can prolong survival with advanced, HER2-positive gastric cancer.1
Radiation therapy involves the use of a particular type of energy, known as ionizing radiation, to kill cancer cells. Radiation can play a role in managing the symptoms of advanced gastric cancer, and can also help to control problems such as bleeding or blockages.
Strategies to Improve Treatment
The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician.
Areas of active investigation in clinical trials of advanced gastric cancer include the following:
Precision Cancer Medicines: Several targeted therapies are being evaluated for the treatment of advanced gastric cancer. These targeted therapies include additional HER2-targeted drugs such as Tykerb® (lapatinib); other types of targeted therapies that have already been approved for other purposes, such as Avastin® (bevacizumab) and Afinitor® (everolimus); and new drugs that are being evaluated in several types of cancer.
Keytruda (pembrolizumab) appears promising in patients with gastric cancer, according results from the KEYNOTE-059 clinical trial. The phase II KEYNOTE-059 is one of the largest studies to investigate immunotherapy in recurrent or metastatic gastric cancer.
Keytruda is a monoclonal antibody that helps to restore the body’s immune system in fighting cancer. It creates its anti-cancer effects by blocking a specific protein used by cancer cells called the programmed death-ligand 1 (PD-L1), to escape an attack by the immune system. Once PD-L1 is blocked, cells of the immune system are able to identify cancer cells as a threat, and initiate an attack to destroy the cancer.
In KEYNOTE 059 25 patients with newly diagnosed metastatic gastric cancer received a combination of keytruda and chemotherapy, and 31 patients with newly diagnosed metastatic gastric cancer received keytruda alone.(2)
In patients with newly diagnosed metastatic cancer, both the combination therapy and keytruda alone were safe and showed some promising activity. These study results are consistent with those reported for Opdivo (nivulomab) another PD-1 inhibitor reported earlier this year and support an emerging role of immunotherapy for selected patients with gastric cancer.(3)
New approaches to chemotherapy: Researchers continue to evaluate new chemotherapy drugs and new combinations of chemotherapy. Some research is also investigating different ways of delivering chemotherapy; intraperitoneal chemotherapy, for example, delivers chemotherapy directly into the abdominal cavity.
- Bang Y-J, Van Cutsem E, Feyereislova A et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010; 376:687-697.
- Abstract LBA28_PR ‘KEYNOTE-059 Update: Efficacy and Safety of Pembrolizumab Alone or in Combination With Chemotherapy in Patients With Advanced Gastric or Gastroesophageal (G/GEJ) cancer.