The pace of progress in cancer research keeps getting faster and faster. However, the results of this research can take time to reach the medical community. The ASCO Plenary Series is a program developed by the American Society of Clinical Oncology (ASCO) to help speed the delivery of high-impact cancer research. In this series, cancer care providers gather online to learn about new, carefully selected research and discuss the study results with their colleagues.
The March 2023 session in the ASCO Plenary Series features this study:
- Zolbetuximab plus chemotherapy can slow cancer growth and help people with advanced gastric or gastroesophageal junction cancer live longer
Follow the discussion about research from the ASCO Plenary Series by using the #ASCOPlenarySeries hashtag on Twitter.
Zolbetuximab plus chemotherapy can slow cancer growth and help people with advanced gastric or gastroesophageal junction cancer live longer
Who does this study affect: People with previously untreated claudin-18.2 (CLDN18.2)-positive, HER2-negative locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma.
What did this study find: The phase 3 GLOW clinical trial found that the targeted therapy drug zolbetuximab given in combination with chemotherapy slowed cancer growth and helped people with previously untreated CLDN18.2-positive, HER2-negative locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma live longer.
Gastric adenocarcinoma, a type of stomach cancer, is cancer that begins in the glands or glandular tissue that lines the stomach. Adenocarcinoma can also occur in the gastroesophageal junction, which is where the stomach and esophagus meet. If the cancer has spread deeper into the tissue layers of the stomach, it is called locally advanced. If the disease has spread to other parts of the body, it is called metastatic. CLDN18.2 is a protein that can be found on cancer cells in the stomach and gastroesophageal junction. Zolbetuximab works by targeting CLDN18.2 on these cancer cells, causing the cancer to slow or stop growing.
Some cancers may make too much of a protein called human epidermal growth factor receptor 2 (HER2). This type of cancer is called "HER2-positive cancer." While there are targeted therapies available to treat HER2-positive stomach cancer, there are no targeted therapies available for treating the majority of patients with HER2-negative disease, including for people with CLDN18.2-positive, HER2-negative gastric or gastroesophageal junction adenocarcinoma. These patients are typically treated with chemotherapy alone. In this study, researchers wanted to learn whether giving zolbetuximab in addition to chemotherapy could slow cancer growth and help patients live longer.
The GLOW study included 507 participants with previously untreated CLDN18.2-positive, HER2-negative locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma. The participants were randomly assigned to receive either zolbetuximab in combination with the chemotherapy drugs capecitabine and oxaliplatin (254 participants) or the chemotherapy drugs with a placebo (253 participants) for 8 3-week cycles. After those 8 cycles, participants continued receiving either zolbetuximab with capecitabine or capecitabine with a placebo until the cancer grew or the treatment side effects became too severe. Most of the participants in the study were from Asia (62% of participants), and the median age of the participants was 60 years. The median is the midpoint, meaning half of the participants were older than 60 and half were younger.
The study found that zolbetuximab combined with chemotherapy slowed cancer growth for longer than chemotherapy alone. Cancer growth was delayed for a median of 8.2 months in the zolbetuximab group compared to 6.8 months in the chemotherapy plus placebo group. Participants in the zolbetuximab group also lived longer, with a median overall survival of 14.4 months compared to 12.2 months in the chemotherapy plus placebo group. Additionally, more participants in the zolbetuximab group had their cancer shrink from treatment (53.8% of participants) than those who received chemotherapy plus placebo (48.8% of participants). The most common side effects in those who received zolbetuximab were nausea, vomiting, and decreased appetite. The rates of serious side effects were similar in both treatment groups.
These study findings were consistent with recent results from the phase 3 SPOTLIGHT clinical trial, which found that zolbetuximab in combination with a different chemotherapy regimen called mFOLFOX6 also slowed cancer growth and helped people with this same type of cancer live longer.
What does this mean for patients: Zolbetuximab given in combination with chemotherapy may be an effective treatment option for people with previously untreated CLDN18.2-positive, HER2-negative locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma.
“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/gastroesophageal junction adenocarcinoma.”
— lead study author Rui-hua Xu, MD, PhD
Sun Yat-sen University Cancer Center