After clinical testing at UCLA, immunotherapy drug approved by FDA to treat stomach cancer

Image of a doctor holding a floating stomach in hand

Pembrolizumab, a drug that has effectively extended the lives of countless people with many types of cancer, has now been approved by the U.S. Food & Drug Administration to treat people with metastatic gastric adenocarcinoma, the most common form of stomach cancer. The research that led to the approval was conducted at UCLA and 67 other sites in the U.S., Europe, South America and Asia.

The drug, marketed as Keytruda, is the first immunotherapy approved by the FDA to treat people with this disease after standard treatments have failed.

“Stomach cancer is particularly challenging to treat, and when the disease progresses to the advanced stages, a cure is no longer possible,” said Dr. Zev Wainberg, one of the leading investigators on this study and a researcher at UCLA’s Jonsson Comprehensive Cancer Center. “Traditional treatments may control the disease for a short period of time, but eventually the tumor will regrow. The approval of pembrolizumab shows that immunotherapy is now a viable option for some of these patients, delivering responses that are long-lasting, and with little to no side effects.”

In the clinical trial, the drug was tested on 257 patients with the disease. Because so many of the patients in the study showed significant long-lasting responses, the FDA granted the drug accelerated approval in stomach cancer.

Pembrolizumab is an antibody that targets the protein PD-1, which is expressed by immune cells. When it binds to another protein called PD-L1, PD-1 acts as an immune checkpoint, dampening the immune system’s T cells which otherwise could attack cancer cells. Some tumors are able to evade an immune response by expressing high levels of PD-L1. So by blocking the interaction between PD-1 and PD-L1, pembrolizumab in effect enables the patient’s immune system to attack the cancer.

In the early and intermediate stages of gastric cancer, doctors can treat patients only in the affected area of the stomach with surgery, or traditional approaches such as chemotherapy and radiation. However, as the cancer progresses and localized treatments do not work, some people may be candidates for systemic therapies, said Wainberg, who also is an associate professor of medicine at the David Geffen School of Medicine and co-director of the UCLA Gastrointestinal Oncology Program.

As the expected survival of patients with metastatic gastric cancer is less than one year, the approval of pembrolizumab now provides encouraging new hope for people whose stomach cancer has progressed on prior traditional and systemic treatments. In this study, the emphasis was on patients who express PD-L1, and the FDA approval is only in these patients. This is an example of a biomarker selected subgroup, which will help allow physicians to better identify patients who can potentially benefit from treatment based on features of their tumors, said Wainberg.

Results of the two-year study showed that overall response rate (the percentage of people in whom tumors were substantially reduced in size) was 12 percent. Among people in the trial that had PD-L1 expression, the overall response rate was nearly 16 percent. In people who responded to treatment, the average duration of response exceeded 12 months, a remarkable advance in this difficult disease. Some people receiving the drug did experience side effects such as fatigue and loss of appetite, but they were generally manageable.

Dr. Michael Teitell, director of UCLA’s Jonsson Comprehensive Cancer Center, said that “this approval marks another milestone as the tenth new indication for pembrolizumab in just three years. This new approval for stomach cancer is a testament to the work of our researchers and the progress we have made in using immunotherapy to treat this disease and other cancers.”

Stomach cancer is among the leading causes of cancer-related deaths worldwide. More than 28,000 new cases of stomach cancer will be diagnosed this year in the United States alone, and about 11,000 people are expected to die of the disease. While fewer Americans are dying from stomach cancer, the disease is much more common in other parts of the world, particularly in less developed countries.

Further research is ongoing to explore combinations of pembrolizumab with other therapies, and help develop new treatment approaches for people with advanced stomach cancer. The goal is that the drug will become the standard of care for these patients in the near future, Wainberg said.