Lung cancer epidemic looming in Asia?

In Asia, however, a lung cancer epidemic is looming as more smokers die and more children take up smoking. Today though, lung cancer is still responsible for more deaths annually in Western countries than breast, colorectal and prostate cancers combined. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for about 80% of all cases, and despite recent advances in treatment, NSCLC remains a disease of poor prognosis, with few treatment options available and an overall five year survival rate of about 15%.

According to a new report* by independent market analyst Datamonitor, despite extensive research and development (R&D) in the field, new drugs may struggle to improve NSCLC patient outcomes. However, research in the field of biomarkers may help improve the treatment of the disease, tailoring therapy to individual patient characteristics.

Bleak prognosis for advanced stage NSCLC patients

In 2008, an estimated 360,000 people in the seven major markets** will be diagnosed with NSCLC. Currently, screening programs are not part of standard clinical practice to routinely detect early development of the disease. As NSCLC is often asymptomatic until it has progressed, the majority of patients will be diagnosed with advanced stage of the disease where treatment has a palliative, rather than curative intent.

The primary risk factor for NSCLC is smoking, which is responsible for more than 85% of all lung cancer-related deaths. The risk for lung cancer increases with the number of cigarettes smoked per day and the number of years spent smoking.

Although the peak of the lung cancer epidemic seems to have passed in the US, Western and Northern Europe, Asia is expected to face a major epidemic in the future, says Datamonitor oncology analyst Deyna Chatzimichalaki. “While the incidence of smoking is decreasing in Western countries, it is increasing in Asia, with more smokers dying and more children taking up smoking.”

Treatment options are limited

Despite recent advances and the increased role of molecular targeted therapies in treatment, NSCLC remains a disease of poor prognosis, with few treatment options available for patients with advanced disease. Surgery can be curative in earlier stages of the disease but patients' older age, associated co-morbidities or advanced disease stage often prohibit its use. As a result, it is estimated that only about 20% of all patients are considered surgical candidates at presentation. Moreover, more than half of patients die of tumor progression after complete surgical resection.

In the management of advanced disease, which is largely based on conventional chemotherapy, the role of molecular targeted therapies is still limited. Genentech/Roche's Avastin is the only targeted therapy to receive approval for the first-line treatment of advanced disease, extending patient median survival when used in combination with chemotherapy, Chatzimichalaki says. “However, due to safety concerns, not all patients are eligible for treatment with Avastin.

“Similarly, other targeted therapies such as Tarceva (OSI Pharmaceuticals/Genentech//Roche/Chugai) and Iressa (AstraZeneca) seem to be more effective only in certain patient populations, thus limiting the number of patients who can truly benefit from treatment,” she says.

Molecular targeted therapies are the focus of development

The high level of unmet need in the treatment of the disease and the large patient population are, however, driving extensive R&D activity in the field of NSCLC. Currently there are over 100 drugs in development, more than half of which are molecular targeted therapies.

Many researchers are of the opinion that an efficacy plateau has been reached with conventional chemotherapy in the treatment of NSCLC. Therefore, most drug developers are investing their resources in the development of novel molecular targeted therapies, in an attempt to improve on the activity and toxicity of chemotherapy. Molecular targeted therapies are the focus of development, accounting for 60% of the entire NSCLC pipeline.

Due to the clinical and molecular heterogeneity of NSCLC, improvements in patient outcomes are likely to arise from targeting multiple signaling pathways, including angiogenesis and apoptosis, Miss Chatzimichalaki says. “This theory seems to be reflected in the NSCLC pipeline, where the majority of molecular targeted therapies are multi-targeted inhibitors.”

Individualised medicine may help improve patient outcomes

It is becoming increasingly clear that NSCLC is a highly heterogeneous disease. This leads to variations in the response to treatment, with survival and sensitivity often being restricted to subgroups of patients. Unfortunately, increasing evidence suggests that new drugs may struggle to improve patient outcomes in unselected patient populations.

In order to maximise the therapeutic potential of novel drugs, developers are currently investigating the field of biomarkers. Biomarkers, when positive, are thought to be predictive for response to treatment, although their correlation with prognosis and survival is less well defined, Chatzimichalaki says. “Their use can help in the selection of patients who have more chances of responding to a particular therapy. Biomarkers may also allow, for example, for the selection of patients who are most likely to recur after surgery and should therefore require post-operative therapy

“This type of individualised medicine - tailoring therapy to patients' clinical or molecular characteristics - may help improve survival for NSCLC patients in the future,” she says.

Notes

*Pipeline Insight: Non-Small Cell Lung Cancer - Pipeline set to offer only modest improvements.
**The seven major pharmaceutical markets are the UK, Japan, France, Germany, Italy, Spain and US.