Lung cancer and its prevalence in China: an Editor Q+A

Cases of lung cancer in China are rising, but why is this? I asked Editors of a new series on lung cancer, Li Yan and Wei Zhang, more about this disease, why its occurrence is increasing in China and the work that is being done to prevent this.


How big a problem is lung cancer?

Globally, lung cancer is the most prevalent and deadly malignancy. It is estimated that 1.8 million new cases of lung cancer are diagnosed every year. Lung cancer has a high mortality rate and accounts for approximately 20% of cancer deaths.

In other words, for every five patients that die of cancer, one is due to lung cancer. We lose around 1.6 million patients because of lung cancer every year. Because of its high incidence and mortality, lung cancer also comprises a large part of the overall economic impact of cancer.

According to the Global Oncology Trend Report, released in May by the IMS Institute for Healthcare Informatics, global spending on cancer medications rose 10.3% in 2014 to $100 billion.

Therefore, lung cancer is a highly prevalent, extremely deadly, and very costly disease and it represents a huge unmet medical need and poses a significant social and economical burden

Lung cancer cases are on the rise in China. Can you tell us more about this?

The World Health Organization’s World Cancer Report 2014 found that China, home to roughly 20% of the global population, now accounts for one-third of global deaths from lung cancer. Multiple factors contributed to the sharp increase in lung cancer cases in China to include air pollution and a large smoking population.

Take Beijing, a city known for its smoggy air, as an example. In 2002, for every 100,000 men living in Beijing, 49 had lung cancer. By 2010, that number had risen more than 50%, to 75. Women in China are less likely to smoke and so have lower rates of the disease.

But among those living in Beijing, a similar sharp rise in lung cancer cases occurred over the last decade. Between 2002 and 2012 for every 100,000 women living in Beijing, the number of women with lung cancer increased from 30 to 46, more than 50%.

The Beijing office of China’s Cancer Prevention and Control Center believes the steep rise in lung cancer occurrences can be linked to worsening air pollution in China’s capital city. One other clue is that the proportion of lung adenocarcinoma cases, those associated with air pollution, is increasing.

How effective are current therapies? Why is there a need for new approaches?

Lung cancer treatment has improved substantially in the past three decades. The introduction of chemotherapy combinations, the so called chemo doublets, has prolonged the survival for patients with late stage lung cancer.

The targeted agents, anti-angiogenesis and epidermal growth factor receptor inhibitors further extended survival benefit. More importantly, the understanding of cancer biology has transformed lung cancer treatment to the era of personalized medicine.

We have yet to find curative approaches to treating late stage lung cancer.

We can now molecularly classify lung cancer patients to subtypes according to the mutations their tumors harbor, and match them with targeted agents specific to treat these mutations. However, we have yet to find curative approaches to treating late stage lung cancer.

After the initial response to chemotherapy or targeted agents treatments, patients inevitably stop responding and their disease relapses or recurs. Immuno-therapies such as check point inhibitors may bring much needed new approaches to treating lung cancer, exemplified by the approval of nivolumab (BMS’ anti-PD1 antibody).

Furthermore, the preliminary yet very encouraging results of atezolizumab (Roche’s anti-PDL1 antibody) plus chemotherapy combination with near 70% response rate in lung cancer suggest great potential for this new class of therapies to become another important pillar of lung cancer treatment in addition to surgery, radiation, chemotherapy, and targeted therapy.

Some of the Perspectives in this series emphasize the importance of more early-phase clinical trials and call for greater global collaboration in this area.  How can this be achieved?

From a drug development perspective, early phase trials are the most scientifically and medically demanding phase of development. Especially in cancer drug development, early phase testing has evolved beyond just defining safety/tolerability and understanding the pharmacokinetics.

Now, an early phase cancer drug trial needs to follow the pharmacodynamic trails to assess whether the drug is hitting the target, how hard and for how long. The study also needs to test the applicability of biomarkers to narrow down sensitive patient population to be tested in late stage confirmatory trials.

A phase I study for cancer drug development can now even evolve quickly to satisfy registration requirements. The successful regulatory approval of pembrolizumab (Merck’s anti-PD1 antibody) based on phase 1 data is such an example.

Early phase trials therefore now require closer global collaboration. To best develop a new cancer drug of which the targeted patient population is prevalent or exclusively found in a geographic area outside of the traditional clinical trial areas, such as the US and western European countries, it would be most efficient to go to the countries where the target patient population can be accessed.

One such example is the development of crizotinib, the anaplastic lymphoma kinase (ALK) inhibitor. The Phase I/II study conducted in South Korea, where there is a relatively higher prevalence of lung cancer patients with EML4-ALK fusion events, approximately 3-5% in East Asia versus 1.5% in western population.

At the moment, how does the carrying out of trials in China and the US differ?

The experience, expertise, skill set, and infrastructure are still lagging in China for early phase drug development in industry, trial sites, as well as regulatory agency.

In China, early phase clinical trials of cancer drugs are yet to mature. This is partly due to the evolving nature of pharmaceutical industry in China from mainly a generic drug industry moving up to become an innovative drug discovery and development industry.

The experience, expertise, skill set, and infrastructure are still lagging in China for early phase drug development in industry, trial sites, as well as regulatory agency. To transform early phase clinical development in China, the near term focus is to gain knowledge and experience as well as trial management skills.

Therefore, the US Chinese Anti-Cancer Association has joined force with industry partners and Chinese Society for Clinical Oncology to advance this very important area of cancer drug development. With the support from numerous US cancer centers, we are confident that a core team of trial physicians, nurses, and relevant staff with global experience in early phase trial conduct and management will be established in China in three years.

This core team will serve as the seeds to further expand the knowledge and best practices throughout cancer centers in China to bring the conduct of early phase oncology trials to global standard to expedite drug development and ensure patient safety, and ultimately bring innovative drugs to our cancer patients in China sooner.

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