Gastric Cancer Care Evolves With Precision Oncology and New Therapies

Dr. Raghav Sundar explained in an interview with CURE how rapid advances in precision oncology are reshaping care for patients with gastric cancer, from earlier-stage treatments to new options in advanced disease.

He highlighted the expanding role of immunotherapy, targeted treatments such as claudin 18.2–directed therapy and the importance of biomarker testing to guide care decisions. Sundar also stressed the need for nutrition support, side effect management and early consideration of clinical trials as part of comprehensive care.

Sundar is an associate professor of internal medicine in medical oncology and hematology at the Yale School of Medicine.

CURE: How have recent advancements in different therapies, such as targeted treatments and immunotherapy, changed the outlook for patients with gastric cancer?

Sundar: Gastric cancer is part of the gastrointestinal tract, and most clinicians who treat gastric cancer also treat other gastrointestinal tumors, such as colon cancer or pancreatic cancer. However, gastric cancer has become more distinct because there have been many new treatments that make it unique in how we approach care. This is largely because precision oncology in gastric cancer has advanced significantly, especially in the past three to five years.

At this point, we divide gastric cancer into very early-stage disease, locally advanced disease, and metastatic or advanced disease, and each is treated differently. In very early-stage disease, we can sometimes perform endoscopic resections, meaning a gastroenterologist can remove the tumor endoscopically without the need for surgery.

In the locally advanced setting, where the tumor is larger but still operable, surgery remains a key part of treatment. For some time now, we have been surrounding surgery with chemotherapy, giving patients a few months of chemotherapy before surgery and a few months after surgery. This approach improves survival and reduces the risk of relapse.

Very recently, including just last year, there has been Food and Drug Administration (FDA) approval for adding immunotherapy to chemotherapy in this setting. Adding Imfinzi (durvalumab), an immunotherapy drug, to chemotherapy has shown improvements in both relapse-free survival, meaning the time before the cancer returns, and overall survival, meaning how long patients live. This is an exciting change, as immunotherapy is now being used even in the locally advanced setting.

In the metastatic or stage 4 setting, there have also been many advances. For several years, immunotherapy has been added to chemotherapy for advanced gastroesophageal cancers, which is a major shift and is somewhat unique compared with other gastrointestinal cancers.

More recently, another target called claudin 18.2 has emerged. This protein is normally present in the stomach lining, where it helps maintain the integrity of the stomach barrier. In cancer, this protein becomes exposed on the surface of tumor cells, making it targetable. A drug called Vyloy (zolbetuximab) targets claudin 18.2, and trials have shown that adding it to chemotherapy improves survival. This drug received FDA approval last year and is now used in patients whose tumors express this marker.

There are also other biomarkers we have used for some time, such as HER2. HER2 is commonly associated with breast cancer, but it is also present in some gastric cancers. We use drugs like Herceptin (trastuzumab) in combination with chemotherapy, and we often add immunotherapy as well, which is something we do in gastric cancer but not in breast cancer.

Overall, this reflects how precision oncology has advanced in gastric cancer. We are identifying the right drugs for the right patients at the right time. Not everyone with gastric cancer is treated with chemotherapy alone anymore, and that is one of the biggest advances in this field.

With these practice-changing treatments in mind, what are some of the most common challenges patients face during treatment, including side effects, nutrition concerns and emotional well-being, and how can these be addressed?

Having cancer and going through cancer treatment is difficult, and everyone experiences different challenges. Gastric cancer is particularly challenging because difficulty eating is not only due to the tumor occupying space in the stomach and causing early satiety, but also because it can reduce stomach motility. Patients often experience abdominal discomfort, nausea and vomiting, which can come from both the tumor and the treatments, as well as fatigue.

Maintaining weight is a major challenge, making nutrition extremely important. Almost all patients treated at Yale are referred to a nutritionist to help with weight maintenance. One common myth is that high-calorie diets feed the tumor. In reality, restricting calories or sugar often worsens weight loss, which can be harmful, because the cancer itself already causes weight loss.

If the cancer spreads, one common site of metastasis is the peritoneum, the lining of the abdomen. This is a difficult area to treat because chemotherapy does not penetrate the peritoneal lining well. These tumors can block the intestines, leading to bowel obstruction, vomiting and, in severe cases, intestinal perforation, which can be fatal.

At Yale, there is a specialized program for patients with peritoneal metastases, involving both medical oncologists and surgeons who specialize in this area. Some patients are offered additional approaches through clinical trials. Treating peritoneal metastases differently from disease spread to the liver or lungs is a concept being explored worldwide.

Another important point is that the drug development space in gastroesophageal cancers is growing rapidly. There are multiple clinical trials available across the United States and at Yale that allow patients access to newer treatments earlier, making clinical trials an important option to consider.

What role do clinical trials play in advancing treatment options for gastric cancer, and how can patients determine whether participation is right for them?

Clinical trials are essential in oncology because they are how we improve upon current treatments. Even today, despite advances, the average life expectancy for advanced gastric cancer is around 18 to 24 months, depending on biomarkers and available treatments. This is much shorter than for cancers like breast or lung cancer, which have more treatment options.

Clinical trials allow us to scientifically test new therapies. Drugs that work in colon cancer or lung cancer do not necessarily work in gastric cancer, so these trials must be conducted specifically in this disease. When a drug is shown to be effective, it becomes another treatment option for patients.

It is especially important to have trials available in the United States. Gastric cancer is more common in Asia, so many trials are conducted there. Having access to these trials in the United States allows patients here to benefit from newer treatments as well.

What key messages would you like to share about awareness and advocacy?

First, it is important to understand and acknowledge the difficult journey patients go through, from early-stage disease to advanced settings. Second, patients should know that newer and better treatments are becoming available. Awareness helps people understand that options exist and that it is worth seeking care and advice, even in advanced disease.

These initiatives are especially important for rare cancers in the United States. They help patients and caregivers know they are not alone and that the medical community is committed to finding the best possible ways to treat these cancers.

Finally, one clarification I want to make is about gastric versus gastroesophageal cancer. Cancers of the esophagus and stomach are divided into adenocarcinomas and squamous cell carcinomas. Squamous cell carcinomas are primarily esophageal cancers. Adenocarcinomas of the esophagus, gastroesophageal junction and stomach are treated similarly and generally follow gastric cancer treatment paradigms.

Some patients are told they have esophageal cancer but are treated like gastric cancer, which can be confusing. In the United States, adenocarcinomas of the lower esophagus and gastroesophageal junction are often managed similarly to gastric cancer, and that distinction is important to understand.

Transcript has been edited for clarity and conciseness.

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