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Immunotherapy Arrives in Gastric Cancer

Angelica Welch
Published: Friday, Mar 30, 2018

Manish A. Shah, MD
Manish A. Shah, MD
In the past year, immunotherapy has emerged as one of the more promising approaches for the treatment of patients with gastric and gastroesophageal junction (GEJ) adenocarcinoma. Specifically, pembrolizumab (Keytruda) and nivolumab (Opdivo) have demonstrated strong clinical activity in this patient population.

State of the Science Summit™ on Gastrointestinal Cancers, Shah, director of gastrointestinal oncology and chief of Solid Tumor Service at Weill Cornell Medicine/NewYork-Presbyterian Hospital, discussed the advancements being made in the treatment of patients with advanced gastric and GEJ cancer.

OncLive: Please provide an overview of your lecture.

Shah: I spoke about immunotherapy in stomach cancer and foregut [carcinoid] tumors like esophageal/GEJ cancers. This is obviously a new treatment for stomach and esophageal cancers, and it has demonstrated some activity in the advanced or third-line setting. Some of the key questions that I addressed were, “Who should be tested for immunotherapy? What is the best test? What is the best marker?”

The other thing I talked about is how we make the immune response even better. We know that the PD-1 inhibitors pembrolizumab and nivolumab work in 10% to 15% of patients with advanced stomach cancers and GEJ tumors. The question is, can you augment that with chemotherapy, radiotherapy, or other immune agents? 

What are your thoughts on moving immunotherapy into earlier settings?

Whether immunotherapy can move up to an earlier setting is a great question. Those studies are being done now. Pembrolizumab was examined against a taxane in the second-line setting, and unfortunately, that was a negative study. Avelumab (Bavencio) was tested in the third-line setting against chemotherapy, which was also negative. In the first-line setting, avelumab was tested as a maintenance approach, in which patients who received chemotherapy were then randomized to receive either chemotherapy or avelumab, and the results of that trial are pending. 

The first-line pembrolizumab as well as and the first-line nivolumab and ipilimumab studies are ongoing, and we should get the results of those in 2019 or 2020. They are also being tested in patients who have locally advanced disease. There is a large registration study looking at chemotherapy with or without pembrolizumab for advanced gastric cancer in the perioperative setting. There are many studies looking at nivolumab with or without ipilimumab in patients with esophageal cancer who received chemotherapy and radiation.

What is the prevalence of microsatellite instability (MSI) in patients with gastric cancer?

Another key area of immune activity is in patients who have a MSI-high (MSI-H) phenotype. That means that they have a high mutation burden. This is also known as Lynch syndrome. Many people don't realize that Lynch syndrome is also associated with gastric cancer. It is most commonly known for [its association with] colon cancer, but it also increases the incidence of gastric cancer.

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