New Frontline Strategies for Advanced Gastric Cancer: Dani Castillo, MD

At the American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium, Dani Castillo, MD, medical oncologist, City of Hope, shared new research titled, “Impact of metastatic sites and Lauren subtype on survival outcomes of first-line PD-1 inhibitors combined with chemotherapy in HER2-negative advanced gastric cancer: a meta-analysis,” that examined clinical outcomes across metastatic subtypes—including liver and peritoneal involvement.

The study underscores both the benefits and limitations of combining chemotherapy with immune checkpoint inhibitors. With standard treatments showing varying effectiveness based on patient heterogeneity, the findings call for tailored therapeutic strategies, prompt referrals to academic centers for cases of extensive peritoneal disease, and early clinical trial enrollment to improve patient outcomes.

This transcript was lightly edited for clarity.

The American Journal of Managed Care® (AJMC®): Can you provide an overview of what this study aimed to examine?

Castillo: Chemotherapy plus immunotherapy has been the first-line treatment in standard settings. When we look at the landmark studies, including 4 to 5 global studies using checkpoint inhibitors with chemotherapy, we know this standard treatment has significantly improved patients’ outcomes in the last decade. However, we also know that gastric cancer is very heterogeneous, and there are different metastatic sites, including liver mass and bone mass. Then, also the environment, and that is a peritoneal disease.

Our main focus on this project is to look at the older network studies. One wants to see the consensus on whether immunotherapy plus chemotherapy has a significant impact on the patient's outcome. However, when we looked at peritoneal disease vs nonperitoneal disease, we found the difference was not significant. When we look at the gastric cancer with the liver mass vs without the liver mass, you can see both types of the gastric cancer benefit from using the chemotherapy and then checkpoint inhibitors.

This is also very interesting to us, because we know that immunotherapy and chemotherapy may not be able to significantly improve patients in this subgroup, so more studies are wanted. And then also we know there are ongoing locoregional treatments, such as HIPEC [hyperthermic intraperitoneal chemotherapy], hopefully in conjunction with those kinds of locoregional treatments, and we will improve patients with gastric cancer with peritoneal disease.

AJMC: What were the key findings?

Castillo: First, gastric cancer is very heterogeneous, even if we call this metastatic gastric cancer. They have different subtypes, and we also know the Lauren histology type plays a role in gastric cancer outcomes. Second, different metastasis means the tumor microenvironment plays a role in the patient's outcome and the treatment response.

AJMC: How could these findings help doctors decide the best first-line treatment for patients with HER2-negative advanced gastric cancer?

Castillo: Very good question. The NCCN [National Comprehensive Cancer Network] guidelines endorsed chemo and immunotherapy in annual receptor metastatic cancer. However, when you have extensive peritoneal disease, the first recommendation you may need to think about, besides chemo and immunotherapy, is that maybe you should refer this patient to a tier 3 and those top-tier academic centers for multidisciplinary programs. Then there are some of the new innovations that can be conducted. And then also, I think there are different immunotherapies.

We know there is tislelizumab, there is pembrolizumab, and there is nivolumab. When you look at the landmark studies, I think the subgroup forest plot has a little difference in terms of the treatment response. However, I think we need a side-by-side comparison between those kinds of immunotherapies for the physicians. We have to have some wellness, and then when you first meet the patient, you need to tell them what the studies are about and what the expectation is.

Gastric cancer, with immune disease so far, has a very bad prognosis, and it depends on whether they will be able to respond to the first-line treatment. Early referrals for clinical trials also are very important.