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Role of Immune Checkpoint Inhibitors in Gastroesophageal Cancer Treatment Landscape


Immune checkpoint inhibitors can play a key role in the treatment of upper-GI and esophageal cancer.

James M. Cleary, MD, PhD: Immunotherapy has made a major impact in the treatment of gastroesophageal cancers. The place where it has probably made the biggest impact for the largest number of patients has been in the treatment of locally advanced esophageal and gastroesophageal junctional cancers. For the longest time, we treated patients with neoadjuvant chemoradiation followed by surgery. It always felt as if we should be doing something after surgery, but all the trials that looked at giving a certain therapy after surgery failed. We had a huge recurrence rate. We always felt as if we should be doing something, but there was no evidence to tell us what to do. This changed in a big way with the advent of adjuvant nivolumab.

Adjuvant nivolumab doubled the disease-free survival of patients who got adjuvant nivolumab compared with placebo control. It has improved our treatment of these patients, and hopefully it’s going to increase the cure rate. The overall survival data aren’t back yet, but we’re all very optimistic about it. It also has helped us enormously in the metastatic setting. Giving PD-1–directed therapy with chemotherapy increases the effectiveness of our treatments. As far as long-term outcomes, some patients do well for years. There are patients with MSI [microsatellite instability]–high gastroesophageal cancers and other cancers, such as patients with EBV [Epstein-Barr virus]–positive gastroesophageal cancers, who seem to do well on PD-1–directed therapy for years. We’re excited about that.

The reason the oncology community—patients and providers alike—has been so enthusiastic about immunotherapy is because when a patient has a great response to immunotherapy, they can respond for years. I have a patient with an MSI-high gastric cancer who has been responding to PD-1–directed therapy for over 4 years. It’s wonderful to see. When I first met him, before we knew that he had an MSI-high tumor, I told him that he’d probably live about a year. To see it was an MSI-high tumor and to see him have such a wonderful response to PD-1–directed therapy that has lasted so long gave us so much hope. The biggest advantage of immunotherapy over traditional chemotherapy is that when it works, it can be very durable, just like the patient we just talked about.

Immunotherapy has been a scientific marvel. For the longest time in cancer research, we didn’t know whether immunotherapy was going to work. There were a lot of dedicated scientists who spent their whole careers trying to prove that immunotherapy could work in cancer. Now it’s obvious to everyone that it can work in a big way. The immune system in our bodies has a very complicated job. Its job is to kill all foreign invaders, such as bacteria and viruses that enter our body that are different from our normal cells. The immune system has to have many safeguards so that it doesn’t attack our normal organs, such as our heart and colon. There’s a lot of regulation on the immune system telling it when to attack foreign bacteria and not to attack your heart.

The problem is that when cancer comes along, cancer is a mix in between. It isn’t exactly normal, but it looks a lot like your normal tissue. The immune system many times misses cancers. But using immunotherapy to stimulate the immune system so that it can recognize that a cancer isn’t normal tissue and kill it off—just as it would kill off a bacteria—has been a major advantage. Over the next few years in oncology, we’re going to get more sophisticated with immunotherapies. My hope is that for gastroesophageal cancer, in 3 or 4 years, there will be even better immunotherapies that can get the immune system to fight off the cancer.

Transcript edited for clarity.

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