Biliary Tract Cancer

Annually, there are approximately 200,000 new cases of biliary tract cancer in Asia, of which up to 145,000 are in China, and approximately 12,600 new cases in the United States [1]. Biliary tract cancer has a five-year survival rate of less than 10% and there has been little improvement in prognosis or treatment outcomes over the last two decades [2].

Biliary tract cancer consists of intra-hepatic and extra-hepatic cholangiocarcinoma (cancer of the bile duct), cancer of the gall bladder and papilla of Vater (the final portion of the bile duct emptying into the small bowel). Though biliary tract cancer is considered to be a subset of liver cancer, therapies approved for liver cancer are not approved for biliary tract cancer. There are no therapies approved for biliary tract cancer in the United States.

Approximately 35% of patients undergo surgical resection, but recurrence is common, with the disease returning in 50% to 60% of patients [3]. Late-stage patients typically receive chemotherapy. In the first-line setting, the doublet combination of gemcitabine and cisplatin is commonly used and has demonstrated a response rate of 26% [4] and overall survival of 11.7 months [5].

Specific pathways driving biliary tract cancer have not been identified, however recent data from Japan and China show that approximately 70% of biliary tract cancer tumours exhibit HER family overexpression, with HER4 expressed most widely [6][7].

We believe that varlitinib has the potential to be the first targeted therapy approved for biliary tract cancer.

Breast Cancer

The prevalence of breast cancer in Asia was approximately 2.3 million patients in 2012, while the prevalence in the United States was approximately 1 million, of which approximately 5% was metastatic in both cases [1].

Metastatic breast cancer has a five-year survival rate of 26% [2]. Approximately 20% of these patients have tumours with HER2 amplification and will typically receive the anti-HER2 monoclonal antibody therapies Herceptin and pertuzumab in first-line treatment and then ado-trastuzumab emtansine in second-line treatment [3]. In third-line treatment, patients receive the HER1/HER2 small molecule inhibitor lapatinib plus capecitabine.

Gastric Cancer

As of 2012, gastric cancer (GC) is the fifth most common cancer and third most common cause of cancer death worldwide [1]. Prevalence was highest in Asia with 1.2 million patients, of which approximately 590,000 were in China [1]. There were approximately 30,000 patients in the United States and 190,000 in Europe [2]. The five-year survival rate is less than 20% [3].

Most patients with gastric cancer are asymptomatic during the early stages of disease, which delays the initial diagnosis. Accordingly, the majority of patients present with advanced disease at initial diagnosis. Surgical resection is still the primary curative treatment for localised gastric cancer, however less than 50% of patients present with localised disease [4]. In the metastatic setting, chemotherapy, such as FOLFOX, XELOX, cisplatin/capecitabine or cisplatin/5-FU, is the standard of care, typically a combination of platinum-based therapy and fluorouridine-based therapy.

Recent advances have demonstrated the role of the HER family of receptors in driving tumour growth. We believe that varlitinib could be effective in treating gastric cancer patients whose tumours are not HER2 amplified, but coexpressed HER1 and HER2. While the coexpression of HER1 and HER2 in gastric cancer is not well documented, epidemiological studies of archived gastric tumours conducted by collaborating institutions in South Korea and Japan suggest that up to 40% of gastric cancer tumours coexpress HER1 and HER2.