A New Antibody Drug Developed for Stage 4 Stomach Cancer Patients Significantly Extends Survival: ASCO 2016

A study presented at the ASCO 2016 Congress, the world’s leading cancer meeting taking place in Chicago these days, has offered hope for treatment of metastatic (stage 4) stomach cancer. According to its results, a first-in-class antibody called IMAB362 was able to increase median survival from 8,4 months to 13,2 months compared with standard chemotherapy.

This treatment targeted the protein called claudin-18 (CLDN18.2), found at high levels in stomach tumors. Claudins are a family of proteins involved in tight junctions between cells. Patients whose tumors showed the highest levels of this protein benefited most from this new treatment.

According to results of the European phase II FAST study, approximately half of patients with stage 4 stomach cancer have abundant CLDN18.2 protein, and these patients are expected to benefit from this new targeted antibody treatment. The protein was also reported to be absent from healthy stomach tissues; thus, as with other targeted drugs, treatment side effects are expected to be very limited.

When antibodies target CLDN18.2 on the cell surface, various cellular and immune responses occur, killing antibody-coated cancer cells. These cellular processes are known as antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity.

The FAST Study

Stomach cancer, with approximately 1 million new patients annually worldwide, is the 5th most common cancer type. The standard initial treatment for stage 4 stomach cancer is chemotherapy. Although adding the targeted drug trastuzumab (Herceptin) provides benefit, Herceptin is used only in HER2-positive tumors, and only about 15% of stomach cancers are HER2-positive.

The study included advanced, that is, metastatic or recurrent stomach and gastroesophageal junction cancer in 161 patients. Their tumor samples had CLDN18.2 levels above a certain threshold. These patients were selected from those who had not previously received any treatment for metastatic stomach cancer and were also ineligible for the HER2-targeted treatment trastuzumab.

Patients were divided into 2 groups;

• one group received only standard chemotherapy, epirubicin, oxaliplatin and capecitabine,
• while the other received IMAB362 together with chemotherapy.

Study Results

Compared with chemotherapy alone, IMAB362 extended median time to disease progression (worsening) from 4.8 months to 7.9 months and median overall survival from 8.4 months to 13.2 months. For patients with the highest CLDN18.2 levels, overall survival was 16.7 months, whereas in this patient group receiving chemotherapy alone it was 9 months.

In conclusion, it is exciting to see immunotherapy working in stomach cancer. It has also been discovered that the CKDN18.2 protein is widely present in tumors other than stomach tumors. It appears that we will frequently hear the name of this cell surface protein and drugs acting on it in the coming period. However, we must state that this new treatment has not entered routine practice, that these are still preliminary results and that for now it is only promising.