Global Collaboration Is Key to Progress in Gastroesophageal Cancers

Christin Melton, ELS
Published: Wednesday, Oct 25, 2017
Johanna C. Bendell, MD
Johanna C. Bendell, MD
The landscape for treating patients with gastroesophageal cancers is undergoing rapid change, and international cooperation among specialists is crucial to the advancement of care, according to a panel of experts who participated in a recent OncLive Peer Exchange® program. The panel, which included experts from the United States, the United Kingdom, and Japan, provided a global perspective on how the management of gastroesophageal cancers is developing. Gastroesophageal cancer encompasses malignancies of the stomach, esophagus, and gastroesophageal junction. Historically, gastroesophageal cancers have posed a tremendous challenge and are associated with low rates of long-term survival.1 New and emerging treatments have the potential to improve outcomes for patients, but limited information is available to guide clinicians on how to incorporate them into care models. “This is a quickly evolving field, and we will have new drugs [or] new treatment options for our patients, and we’ll need to be smart about how to sequence them,” said panel member Manish A. Shah, MD.

Gastroesophageal Cancer Outcomes: East Asia Versus Western Countries

Johanna C. Bendell, MD, who served as moderator for the panel, pointed out that the main subtypes—gastric, esophageal, and gastroesophageal junctional carcinoma (GEJC)—are distinctly different diseases. Shah said most cases of gastroesophageal cancer are caused by helicobacter pylori (H pylori), a bacterium found in the stomach lining that affects half the world’s population. Cigarette smoking is another major risk factor.1 Identification and treatment of H pylori and declines in smoking rates have led to reductions in the incidence of gastric cancer in developed countries, but it remains a significant problem worldwide. Conversely, the incidence of GEJC continues to climb in developed and underdeveloped countries.2

“Depending on what part of the world you’re in, your gastroesophageal cancer may have a different prognosis, behavior, and response to therapy,” Bendell said. It is widely recognized that the prevalence of gastric cancer is much higher in East Asian countries such as Japan and China than in Western countries, yet survival outcomes are typically better in the East.3

Kohei Shitara, MD, said that despite the decrease in prevalence, “[Japan] still has 50,000 new gastric cancers, at best, annually.” As a result, Japan has implemented nationwide screening programs, which Shitara said means approximately 70% of gastric cancers are diagnosed at an early stage.

Ian Chau, MD, FRCP, said nationwide screening programs would not be cost effective in Europe or the United States, where gastric cancer is relatively uncommon. As a result, most patients in Western countries present with locally advanced disease, Shah said. Chau added that they are typically also older than Japanese patients at diagnosis and thus less able to tolerate intensive therapies.

“Historically, D2 gastrectomy is a standard surgical procedure for Japanese gastric cancer, and it achieves almost a 50% disease-free survival without any type of chemotherapy,” Shitara said. Shah said the survival rate with surgery alone is 30% or less in the United States and Europe, underscoring the differences in the disease between East Asian and Western countries.

“It’s a completely different ball game,” said Yelena Y. Janjigian, MD. Because of the differences, drug trials in Asian patients are routinely considered inapplicable to Western populations. That perspective may be evolving, however, after reports from clinical trials of checkpoint inhibitors showed similar response rates and survival outcomes in East Asian and Western patients.

Immunotherapy Trials

In the phase III ONO-4538-12 (ATTRACTION-2) trial, patients from Japan, Korea, and Taiwan with advanced gastric cancer or GEJC were randomly assigned to salvage therapy (third or later line) with nivolumab (Opdivo) monotherapy (n = 330) or to placebo (n = 163) until unacceptable toxicity or disease progression.4 According to an interim analysis, the nivolumab arm had a significantly higher objective response rate (ORR) than the placebo arm (11.2% vs 0%, respectively; P <.0001) and a significantly longer median progression-free survival (PFS; 1.61 vs 1.45 months, respectively; P <.0001).4 The median duration of overall survival (OS) was 5.32 months in the nivolumab group versus 4.14 months in the placebo group, representing a 37% reduction in the risk of death with nivolumab (HR, 0.63; 95% CI, 0.50-0.78; P <.0001).

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