ASCO Expert Perspective 
“Together, the results of the GLOW and SPOTLIGHT trials are poised to change the treatment landscape for patients with CLDN18.2-positive/HER2-negative advanced gastric/gastroesophageal junction cancer. In the United States, the current standard of care for first-line treatment of advanced esophagogastric adenocarcinoma is platinum/fluoropyrimidine plus nivolumab. Therefore, the biggest question this trial raises is how zolbetuximab will compare or combine with checkpoint inhibitors.”
– Pamela L. Kunz, MD, ASCO Expert in Gastrointestinal Cancers

Zolbetuximab in combination with chemotherapy extends survival in patients with 1L claudin-18.2-positive/HER2-negative locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. These results will be presented during the March 2023 session of the American Society of Clinical Oncology (ASCO) Plenary Series. 

CLDN18.2 is a protein found on cells in the stomach and in the gastroesophageal junction. Zolbetuximab binds to CLDN18.2 on cancer cells, causing cancer cell death. CLDN18.2 status is not routinely evaluated in patients with locally advanced resectable or metastatic gastric/GEJ adenocarcinoma, and there is currently no approved therapy for these patients.

In the GLOW study, 507 patients were randomized 1:1 to receive zolbetuximab along with a chemotherapy regimen of capecitabine plus oxaliplatin (CAPOX) or placebo with CAPOX. After eight cycles, patients continued with zolbetuximab or placebo, plus capecitabine, until disease progression or a discontinuation criterium was met. Progression-free survival (PFS) was a median of 8.2 months in the zolbetuximab group compared to 6.8 months in the placebo group. Overall survival (OS) was a median of 14.39 in the zolbetuximab group compared to 12.1 months in the placebo group.

The authors recently presented findings from the SPOTLIGHT trial at the 2023 ASCO Gastrointestinal Cancers Symposium. That study found that patients with CLDN18.2-positive/HER2-negative locally advanced or metastatic gastric/GEJ adenocarcinoma treated with zolbetuximab and folinic acid, 5-FU, and oxaliplatin (mFOLFOX6) had better PFS and OS compared to those treated with placebo and mFOLFOX6.

According to the authors, platinum/fluoropyrimidine chemotherapy is one of the standard first-line therapies for patients with HER2-negative, locally advanced unresectable or metastatic gastric/GEJ adenocarcinoma, but there is no consensus among the available guidelines on the specific regimen that should be used in clinical practice. To account for this, the authors selected standard approved chemotherapy regimens used globally in combination with zolbetuximab—mFOLFOX6 in the SPOTLIGHT trial and CAPOX in the GLOW trial.

“The results of GLOW and SPOTLIGHT suggest that zolbetuximab plus chemotherapy has the potential to be an innovative therapeutic option and a potential new standard of care for patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric/GEJ adenocarcinoma,” said lead GLOW study author Rui-hua Xu, MD, PhD from Sun Yat-sen University Cancer Center in Guangzhou, China.

Abstract and presentation will be available here on March 22, 2023, at 4:00 pm ET

View Expert Disclosures: https://coi.asco.org/share/TLS-NHXP/Kunz%2c%20Pamela

View Author Disclosures: https://coi.asco.org/Report/ViewAbstractCOI?id=405736

ATTRIBUTION TO THE ASCO PLENARY SERIES IS REQUESTED IN ALL COVERAGE.

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