Treatment of Recurrent Gastric Cancer
Medically reviewed by C.H. Weaver M.D. Medical Editor 10/2018
Patients with recurrent gastric cancer have cancer that has returned after primary treatment. Patients with refractory gastric cancer have cancer that has stopped responding to primary or secondary treatments. Both are rarely treated with surgery and systemic treatment with chemotherapy, precision cancer medicines or participation in a clinical trial is typically offered.
The following is a general overview of the treatment of recurrent or refractory gastric cancer. Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied. The information on this Web site is intended to help educate you about your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.
Chemotherapy is the main treatment for patients who have residual cancer after surgery or experience a cancer recurrence after surgery. 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 and prior treatments. Chemotherapy may be used alone or in combination with other treatments such as targeted therapy, radiation therapy, and/or surgery.
Precision Cancer Medicines
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)
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.
The investigators reported an overall objective response rate of 12% with keytruda treatment alone in the pretreated patients and the patients who expressed PD-L1 were more likely to respond than those who did not, with objective response rates of 16%.
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.
Lynparza is a poly ADP-ribose polymerase (PARP) inhibitor that blocks enzymes involved in repairing damaged DNA. Lynparza was initially approved for treatment of women with advanced ovarian cancer associated with defective BRCA genes in 2014.
In a Korean study 124 patients were treated with either oral Lynparza plus paclitaxel or placebo plus paclitaxel followed by maintenance monotherapy with Lynparza or placebo.
The combination of Lynparza/paclitaxel was generally well tolerated, with no unexpected side effects. The researchers reported significantly improved survival for the combination compared to placebo/paclitaxel in the overall study population. The combination also significantly improved survival versus placebo in patients with low ATM expression.(4)
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.
For patients with recurrent gastric cancer, surgery may be performed in order to reduce bleeding or to keep the cancer from obstructing the intestines or stomach. To learn more about surgical treatment, go to Surgery and Gastric Cancer.
Prior to any surgical procedure, adequate preparation of the patient is important to minimize complications. Many patients with gastric cancer are malnourished at the time of diagnosis. Aggressive nutritional support has not been shown to improve long-term survival, but it has been shown to improve survival in the immediate post-operative period. Feeding intravenously and/or through a naso-gastric tube can enhance nutrition before surgery.
Strategies to Improve Treatment
The progress that has been made in the treatment of gastric cancer has resulted from the use of multi-modality treatment and improved patient and physician participation in clinical trials. Currently, there are several areas of active exploration aimed at improving the treatment of gastric cancer.
New Chemotherapy Regimens: Development of new multi-drug chemotherapy treatment regimens that incorporate new or additional anti-cancer therapies for use as treatment is an active area of clinical research carried out in phase II clinical trials in patients with stage IV or recurrent gastric cancer. Clinical trials evaluating new chemotherapy combinations combined with precision cancer medicines are a major focus of research.
Phase I Trials of Chemotherapy: New chemotherapy drugs continue to be developed and evaluated in phase I clinical trials. The purpose of phase I trials is to evaluate new drugs in order to determine the best way of administering the drug and to determine whether the drug has any anti-cancer activity in patients with gastric cancer. Phase I trials are usually performed in patients with recurrent or refractory cancer.
New Targeted Therapies: 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.
- 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.
- Yung-Jue Bang, MD, PhD et al. online in the Journal of Clinical Oncology.