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PubMed This is a summary of 20 peer-reviewed journal articles Updated
Oncology

What Does Claudin 18.2 Positive Mean for Gastric Cancer?

At a Glance

A Claudin 18.2 positive biomarker means your diffuse gastric cancer cells have high levels of a specific surface protein. This is good news, as it makes you eligible for zolbetuximab (Vyloy), a targeted therapy that specifically hunts and attacks these cancer cells when combined with chemotherapy.

In this answer

4 sections

01

What is Claudin 18.2?

02

How Does a Positive Result Change My Treatment?

03

What to Expect: Managing Side Effects

04

Looking Ahead

If your oncologist told you your diffuse gastric adenocarcinoma is Claudin 18.2 positive (often written as CLDN18.2), it means your cancer cells have high levels of a specific protein on their surface. Finding this biomarker is an important and positive development for your treatment plan [1]. For patients whose tumors have this protein and are negative for another protein called HER2, it opens the door to a new targeted therapy drug called zolbetuximab (brand name Vyloy) [2]. Zolbetuximab is designed to specifically hunt down and attack cells carrying the CLDN18.2 protein, offering a personalized way to treat advanced stomach cancer [3].

What is Claudin 18.2?

Claudins are proteins that normally help hold healthy cells tightly together. However, when normal stomach cells turn into cancer cells, the CLDN18.2 protein becomes exposed on the outside of the cell surface [4]. Because it sits on the surface of the cancer cells, it acts like a target that specialized drugs can aim for [5].

This protein is frequently found in gastric adenocarcinomas, including the diffuse subtype [6]. To determine if your tumor has this biomarker, a pathologist performs a specialized test on your biopsy tissue called immunohistochemistry (IHC) [7]. The FDA-approved test used to identify eligible patients is called the VENTANA CLDN18 (43-14A) RxDx Assay [8]. A tumor is considered “positive” if 75% or more of the cancer cells show moderate to strong levels of this protein.

How Does a Positive Result Change My Treatment?

A positive CLDN18.2 test fundamentally expands your treatment options. Until recently, standard chemotherapy was the main option for many patients. Now, patients with CLDN18.2-positive, HER2-negative, advanced or metastatic stomach cancer can receive zolbetuximab [9].

Zolbetuximab is the first and currently only approved targeted therapy for this specific biomarker [2]. It is given as an intravenous (IV) infusion at your cancer center, typically alongside standard chemotherapy regimens such as mFOLFOX6 or CAPOX, as your first-line treatment [10].

Two major phase 3 clinical trials, known as the SPOTLIGHT and GLOW trials, proved the effectiveness of this new drug. These trials showed that adding zolbetuximab to standard chemotherapy significantly improved both how long patients lived (overall survival) and how long they lived without their cancer growing (progression-free survival) compared to using chemotherapy alone [11][12]. This integration of zolbetuximab provides a powerful new therapeutic alternative for advanced gastric cancer [13].

What to Expect: Managing Side Effects

Because the CLDN18.2 protein is also found in healthy stomach cells, targeting it can cause side effects related to your digestive system.

The most common side effects of zolbetuximab are nausea and vomiting, which are often most intense during your first treatment cycle [14]. Fortunately, these side effects are highly predictable and manageable. Your oncology team will give you strong, proactive anti-nausea medications (antiemetics) before and during your IV infusion to prevent you from feeling sick [15][16].

In less common instances, the drug can cause mucosal alterations (changes to the stomach lining) or a condition where protein is lost through the gut, leading to low protein levels in the blood [17][18]. Your doctors will monitor your bloodwork closely to catch and manage these issues early [19]. You should also watch for physical symptoms of low protein, such as unexplained fatigue or new swelling in your legs and ankles, and report these to your care team immediately.

Looking Ahead

Zolbetuximab is a monoclonal antibody—a drug that mimics your immune system to attack specific cells. Because CLDN18.2 is such an effective target, researchers are also testing other innovative therapies in clinical trials, such as bispecific antibodies and CAR-T cell therapies, to find even more ways to fight CLDN18.2-positive stomach cancer [3][20].

Common questions in this guide

What does it mean if my stomach cancer is Claudin 18.2 positive?
It means your cancer cells have high levels of the CLDN18.2 protein on their surface. This is a positive finding because it acts as a target for specific new treatments to track down and attack the cancer cells.
What is the treatment for Claudin 18.2 positive diffuse gastric cancer?
Patients who are CLDN18.2 positive and HER2 negative can be treated with a targeted therapy drug called zolbetuximab. It is typically given as an intravenous infusion alongside standard chemotherapy regimens like mFOLFOX6 or CAPOX.
What are the side effects of zolbetuximab?
The most common side effects are nausea and vomiting, especially during the first treatment cycle. Because this is predictable, your oncology team will give you strong anti-nausea medications before your infusion to help prevent you from feeling sick.
How do doctors test my tumor for Claudin 18.2?
A pathologist performs a specialized test on your biopsy tissue called immunohistochemistry (IHC). Your tumor is considered positive if 75% or more of the cancer cells show moderate to strong levels of the CLDN18.2 protein.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.What was the specific percentage score of my tumor's Claudin 18.2 IHC test?
  2. 2.Has my biopsy been tested for both HER2 and CLDN18.2 to confirm my eligibility for zolbetuximab?
  3. 3.Which standard chemotherapy regimen (such as mFOLFOX6 or CAPOX) do you recommend pairing with zolbetuximab for my treatment?
  4. 4.What will my specific IV infusion schedule look like, and how long does each appointment take?
  5. 5.What is the specific anti-nausea protocol we will use to prevent gastrointestinal side effects during my first treatment cycle?

Questions For You

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References

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This information about Claudin 18.2 testing and targeted therapies is for educational purposes only. Always consult your oncologist to understand what your specific biomarker results mean for your treatment plan.

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