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The Current and Future Management of Gastric Cancer With David H. Ilson, MD, PhD
David H. Ilson, MD, PhD

The Current and Future Management of Gastric Cancer With David H. Ilson, MD, PhD

David H. Ilson, MD, PhD
AJMC®: What is the burden of gastric cancer in the United States? How does it differ from the burden of gastric cancer in other countries? How has treatment changed over time?
Dr Ilson: This is actually a disease that has decreased in incidence in the last century. One hundred years ago, gastric cancer was one of the leading causes of cancer in the United States. And over the last century, it has continued to decline in incidence, probably due to better food storage conditions. We used to have salted and smoked foods. Now, we have better refrigeration and better food handling. Also, there has been a decline in the population incidence rate of Helicobacter pylori infection. H. pylori infection is probably the leading cause of gastric cancer globally, and that has decreased in incidence in the United States.

I think those factors have led to a fairly dramatic drop in incidence of gastric cancer. Despite this, gastric cancer is still not an uncommon disease. We see about 24,000 Americans a year that develop this cancer, and then if we factor in esophageal cancer, which is right next door and accounts for 17,000 cases, we are talking about more than 40,000 combined cases of gastric cancer and esophageal cancer in the United States each year. But individually, gastric cancer occurs with an incidence less than 10% to 15% of the incidence seen with more common cancers we screen for, so there is no effective screening for this disease in the United States. That is in comparison to East Asia, where it is one of the most common cancers, certainly in Korea and Japan. Because it is a leading cause of cancer-related death, they have screening programs in Japan and Korea that probably lead to earlier detection in comparison to the West, where patients usually present with symptomatic disease. As a result, there is no effective screening in the United States. Gastric cancer is a disease that is decreasing in incidence, and so, as a consequence [of less awareness and less screening], most patients present with locally advanced disease and up to 30% to 40% of patients present with metastatic disease even at diagnosis.
AJMC®: Treatment is generally surgical, followed by chemotherapy in many cases. However, there remains some nonstandardization of care and uncertainties among clinicians in appropriate chemotherapeutic regimen selection. Can you discuss the lack of standardization of care in gastric cancer?
Dr Ilson:  Yes, I think it is becoming more standardized. Standard staging would be endoscopy, computer-aided tomography scan imaging, and then laparoscopic staging to rule out metastatic disease. Patients who have early-stage disease—stage I—would be candidates for primary endoscopic surgery or upfront surgery alone. In patients who have stage II or III disease, we typically consider perioperative chemotherapy, which involves administering chemotherapy before and after surgery. That has become a standard since the mid-2000s based on data from the United Kingdom—the MAGIC trial—that shows that perioperative chemotherapy improves survival by about 14% to 15% and reduces the risk of recurrence by 30%.

In Asia, culturally, they prefer to do surgery up front and then give adjuvant chemotherapy for 6 months to a year. In Japan, they give a year of S1, which is an oral 5-fluorouracil equivalent. In Korea, they showed that 6 months of capecitabine and oxaliplatin also conveyed survival benefits. And, considering all these approaches, adding chemotherapy to surgery improves survival outcomes by about 10% to 15%, which translates into about a 30% reduction in the risk of recurrence.

In Europe and the United States in academic centers, we would do perioperative chemotherapy. The old standard used to be ECF (epirubicin combined with cisplatin and infused 5-fluorouracil), with substitution of oxaliplatin for cisplatin or capecitabine for 5-fluorouracil in some cases. Recent studies have suggested that epirubicin may not add a benefit to chemotherapy. And there is going to be a major presentation at the American Society of Clinical Oncology (ASCO) meeting [of a study] that looked at 5-fluorouracil and oxaliplatin with Taxotere (docetaxel) that might have resulted in better survival than ECF perioperatively, so it is possible that a taxane triplet regimen may become the new standard of care once the data are presented at ASCO.

I think there is a consensus that patients should get surgery and should get preoperative and postoperative chemotherapy, or adjuvant chemotherapy, if they have had good surgery. There is increasing controversy about whether or not postoperative radiation adds any benefit. There was a trial in Korea where they randomized patients after surgery to get chemotherapy alone or chemotherapy sandwiched with radiation, and there was no survival benefit for adding radiation. This was a trial of 500 to 600 patients.

And then there was a recent European study called the CRITICS trial, which has not been published yet, but that also looked at adding adjuvant radiation after gastrectomy. All the patients received perioperative chemotherapy, like the European and US [approaches]—preoperative and postoperative chemotherapy around surgery—and then patients were randomized to get or not get the addition of postoperative radiation. That trial also showed no survival benefit for adding radiation.

For gastric cancer, perioperative chemotherapy or adjuvant chemotherapy are standards, and it is not clear whether adjuvant radiation adds any benefits. The current research questions are looking at new drugs, so there are trials looking at adding trastuzumab to perioperative chemotherapy. There is also a trial in Europe looking at dual HER2-targeted therapy combining pertuzumab with trastuzumab and perioperative chemotherapy. There is also going to be a trial opening within the next year looking at immunotherapy added to perioperative chemotherapy with anti-PD1 therapy with pembrolizumab. That trial is in development.

That is where we are right now. I think the focus on drug development right now is HER2-targeted agents and immunotherapy drugs, but there are no data to report yet.

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