Will immunotherapy add value to chemotherapy for HER-2 positive gastric cancer?

The prognosis for patients with gastric cancer is poor. In western countries even patients with localized gastric or gastro-esophageal junction adenocarcinoma are faced with 5-year survival rates of approximately 35% after standard perioperative chemotherapy and curative surgery.

For some of these patients, however, there might be a more effective treatment plan: 10-20% of gastric cancers overexpress the Human epidermal growth factor receptor 2 (HER-2). In patients with advanced HER-2 positive gastric cancer, addition of the monoclonal antibody trastuzumab to standard chemotherapy improves survival significantly.

In HER-2 positive breast cancer, trastuzumab is a standard of care since more than a decade for both palliative, neoadjuvant and adjuvant treatment. Furthermore, addition of trastuzumab to standard neoadjuvant chemotherapy significantly improves both pathological complete response rates as well as overall survival in patients with HER-2 positive breast cancer.

Now, EORTC trial 1203—INtegratioN of trastuzumab, with or without pertuzumab, into perioperative chemotherapy of HER-2 posiTIve stomach cancer, is open for recruitment for patients with early, HER-2 positive gastric cancer. This phase II, randomized EORTC study was developed to investigate the added value of a perioperative treatment regimen which includes HER-2 targeting drugs for patients with gastric and gastro-esophageal junction cancers.

Dr. Anna Dorothea Wagner of Centre Hospitalier Universitaire Vaudois—Lausanne in Switzerland and Coordinator of this study points out, "Considering that HER-2 targeted treatment with trastuzumab has been shown to improve survival in early, HER-2 positive breast cancer when given in addition to chemotherapy either before (neoadjuvant) or after surgery (adjuvant), as well as in patients with advanced, HER-2 positive gastric cancer, I found it difficult not to administer this drug in patients with early, HER-2 positive gastric cancer when we know that efficient systemic therapy increases the chance for long-term survival. For this reason I proposed this trial."

This phase II, randomized EORTC study was developed to investigate the added value of a perioperative treatment regimen which includes HER-2 targeting drugs for patients with gastric and gastro-esophageal junction cancers. Considering that between 10 to 20% of patients with gastric and gastro-esophageal cancer are HER-2 positive, adding the antibody trastuzumab to chemotherapy is likely to prove beneficial for this subset of patients.

Patients in the standard arm will receive cisplatin and capecitabine or 5-FU chemotherapy before and after surgery.

Patients in the first experimental arm will receive chemotherapy just like the control group, but in addition they will also receive trastuzumab at day one of every chemotherapy cycle and this immunotherapy will be continued after the end of chemotherapy for a total of one year.

Patients in the second experimental arm will receive chemotherapy plus trastuzumab as in the first experimental arm, but they will also be given pertuzumab on day one of every chemotherapy and trastuzumab cycle. This treatment will continue after the end of chemotherapy for a total one year in combination with trastuzumab.