Targeting Angiogenesis

An unmet need in gastric cancer

Author

Wong Seng Weng

Medical Director & Consultant Medical Oncologist The Cancer Centre, Paragon Medical & Mount Elizabeth Novena Specialist Centre, Singapore

More about Author

Wong Seng Weng is currently the medical director and consultant medical oncologist of The Cancer Centre, and a visiting consultant of Mount Elizabeth Hospital, Mount Elizabeth Novena Hospital and Gleneagles Hospital in Singapore. His sub-specialties include breast cancer, lung cancer and gastrointestinal cancers. Dr Wong obtained his basic medical degree from the National University of Singapore (NUS) under the Lim Boon Keng and Tan Siak Kew Scholarships. He completed his post-graduate training in Internal Medicine and obtained his membership of the Royal College of Physicians of the United Kingdom (MRCP UK). In the area of research, he holds the appointment of adjunct clinician scientist of the Institute of Bioengineering and Nanotechnology (IBN) in the Agency for Science, Technology and Research (A*STAR).

Gastric cancer is the fifth most common cancer in the world and the third-leading cause of cancer-related deaths. Asia in particular has the highest incidence rates and remains a significant public health problem as it often presents itself at the advanced stages with poor prognosis. The focus of research on new therapeutic strategies has moved from standard chemotherapy agents to designing agents that would target specific receptors and pathways. Encouraging developments and results from significant clinical trials have injected new hope of increased survival for patients. How does this impact the way advanced gastric cancer is treated?

Targeted therapy for disrupting tumour blood circulation - anti-angiogenesis – has finally found its place under the sun in advanced gastric cancer.

Despite the declining incidence of gastric cancer worldwide, statistics from the International Agency for Research on Cancer (GLOBOCAN 2012) showed that, nevertheless, close to a million new cases are diagnosed annually worldwide making gastric cancer the fifth biggest cancer scourge on the globe. Coupled with a mortality rate in excess of 65 per cent, gastric cancer stands today as the third most common cause of cancer death around the world. East Asia and Southeast Asia, in particular, carry more than their fair share of this disease burden given the relatively higher incidence of gastric cancer in these regions compared with the rest of the world.

Precious little progress has been made over the last decade in the field of chemotherapy for stage IV gastric cancer (stage IV being the commonest stage at diagnosis worldwide) beyond the use of a platinum analog and fluoropyrimidine cytotoxic doublet as first line treatment.

While survival has reached crescendo after crescendo in other major cancer types such as breast cancer, colorectal cancer and lung cancer with beaucoup success stories in research, gastric cancer has been very much of a laggard.

The results of the ToGA trial in 2010 demonstrating the benefit of the addition of a monoclonal antibody–tastuzumab-in the subgroup of advanced gastric cancers with amplification of the Human Epidermal growth Receptor 2 (HER2) represented the first major breakthrough beyond platinum and fluoropyrimidine. This HER2 over-expressing subgroup, however, forms only about a quarter of all advanced gastric cancer encountered in the clinical setting. Hence, this strategy was not widely applicable.

Breakthrough in Anti-Angiogenesis Strategy

2014 brought more good news by way of the REGARD and RAINBOW trials firmly establishing the role of ramucirumab (Cyramza®) and the importance of anti-angiogenesis in the treatment of advanced gastric cancer beyond first line.