This is Part 2 of the cover story on Pharmaceuticals: Links to Part 1, Part 3

The incidence of cancer is rising in Taiwan as the population rapidly ages. In 2013 (the most recent year for which statistics are available), 99,143 Taiwanese were diagnosed with cancer, an increase of 2,449 people from 2012, according to a report published in April by the Health Promotion Administration (HPA) under the Ministry of Health and Welfare. The median age at which cancer was diagnosed was 62.

The HPA report found that colon, lung, liver and breast cancers were the most common types of the disease afflicting the Taiwan population. Each of those four illnesses affected more than 10,000 people in 2013, together comprising more than 50% of overall cancer cases.

According to data compiled by the World Health Organization (WHO), Taiwan has the world’s highest prevalence of colorectal cancer. In 2012, 14,965 new cases of colorectal cancer were reported, an eleven-fold increase over the number in 1979.

An increased incidence of lung cancer among Taiwanese women is of particular concern. The disease is now the leading cause of death among the island’s female population. In 2013, a total of 3,141 Taiwanese women died from lung cancer, according to the Formosa Cancer Foundation. Among female non-smokers, the incidence of lung adenocarcinoma has increased fivefold since the early 1990s.

Lung adenocarcinoma is one of the deadliest cancers because it typically shows no symptoms in its early stages. By the time it is discovered, the disease is often at an advanced stage and has spread to other body organs.

A 2014 study by the National Health Research Institute (NHRI) suggests that exposure to secondhand smoke may increase the risk of developing lung cancer by a factor of 1.32. When there is exposure both at home and at work, the risk increases by a factor of 1.73. The percentage of Taiwanese women exposed to secondhand smoke rose from 26.3% in 2008 to 28.5% in 2014, according to the study. The NHRI research also showed that regular exposure (at least 144 times in a year) to a poorly ventilated cooking environment increases lung cancer risk by 178%.

James Yang, director of the Graduate Institute of Oncology at National Taiwan University (NTU) Hospital, says the increase in cases of lung cancer in non-smokers is not unique to Taiwan. The incidence of lung cancer in non-smokers in East Asia, including Japan, Korea, Thailand and the Philippines, has been gradually increasing since about 1995, he notes. The prevalence of the disease in East Asians may be linked to their genetic makeup, he adds.

Pioneering treatment

Taiwan has played an important role in developing targeted therapy to treat lung cancer, Yang observes. In 2000, he was part of a team of scientists at NTU that was among the first in the world to do a targeted therapy study with gefitinib, an epidermal growth-factor receptor (EGFR) inhibitor. EGFR is a protein on the surface of cells that helps them grow and divide. As some lung cancer cells have excessive EGFR, they grow at an uncontrollable rate. By interrupting signaling through the EGFR in target cells, gefitinib prevents cancerous cells from growing and multiplying.

During the study, the scientists found that lung adenocarcinoma patients who had previously failed to respond to chemotherapy responded well to gefitinib. In 2004, Yang and his colleagues discovered a link between the positive response of East Asian lung cancer patients to gefitinib and the frequency of EGFR mutation in the tumors.

The scientists then initiated clinical trials. In East Asian EGFR mutation-positive patients, they found that gefitinib proved to be more effective than chemotherapy in boosting progression-free survival. Yet the researchers also found that chemotherapy was more effective than gefitinib if EGFR mutation was not present in a patient’s tumor.

“This was a pioneering study that changed the way we diagnose and treat advanced-stage lung cancer patients,” Yang says. Beginning in 2007, Yang and his colleagues launched trials using afatanib, a drug which Taiwan played a key role in developing. In addition to NTU Hospital, five other Taiwanese medical centers researched the drug: Tri-Service General Hospital, National Cheng Kung University Hospital, Taipei Veterans General Hospital, Chang Gung Memorial Hospital, and Chiayi Chang Gung Memorial Hospital.

Afatinib differs from gefitinib in that it blocks HER2 – a protein on the surface of cells similar to EGFR – as well as EGFR. Furthermore, because afatinib attaches permanently to the tyrosine kinase (enzymes responsible for the activation of many proteins) in the EGFR and HER2, it is considered more potent than gefitinib.

Following successful global Phase II and III studies, afatinib was approved in many countries as a front-line treatment for metastatic non-small cell lung carcinoma (NSCLC).

A single dominant driver mutation gene that controls tumor growth appears to be common in lung cancer patients, Yang notes. Impeding that gene “often leads to tumor regression [a decrease in tumor size or in the magnitude of cancer in the body] and long progression-free survival,” he says,

Still, in many cases, the cancer resists targeted therapy, Yang says. And at present, there is still no effective method to identify high-risk individuals and screen them for lung adenocarcinoma. As surgery is usually impossible in the late stages of lung cancer, the disease is particularly lethal, he notes. While survival rates are expected to gradually improve over the next decade, “for now, finding a cure for lung cancer remains elusive,” he says.