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Clinical utility of and access to cancer molecular diagnostics in Asia
What’s in it for me? Learn how molecular diagnostics can or cannot transform the care for cancer patients in Asia
by Dr Allen Lai and Dr Maarja-Liisa Nairismagi

With the growing cancer burden, the need to rethink how cancer is fought across Asia has never been more apparent. The introduction of precision medicine, together with the development and availability of next generation diagnostic tools, has shed light on how disease management can be more efficient, more personalized and most importantly, cheaper in the long run. For example, the technology of high throughput molecular diagnostics has revolutionized personalized healthcare because it generates massive sequencing data in a single test with minimal specimens required. As this movement is starting to take shape in Asia, it is pertinent to critically review the access to molecular diagnostics and targeted therapies in the region.

In this article, we will walk you through the unmet clinical needs in cancer management in Asia, how and why it is paramount to use molecular diagnostics in supporting doctors to translate genomic information into a tailored treatment option and to make the best therapeutic decision for their patients.

Cancer burden in Asia – a tremendous number of unmet needs

Cancer is the biggest cause of mortality worldwide with 8.2 million deaths in 2012 . Asia has become the hotspot of cancer development with a tremendous number of new cases diagnosed each year. Looking specifically at Southeast Asia, it is estimated that there were over 770,000 new cases of cancer and 527,000 cancer deaths in the region in 2012. Dismally, the number of new cases per year is expected to dramatically rise by about 70% by 2030, to reach 1.3 million.

Among all, Asia astonishingly carries a disproportionate burden of worldwide liver, esophageal and gallbladder cancer cases. Altogether, three quarters of all new liver cancer cases in males and two thirds in females occur in the fifteen Asian countries. More than 70% of newly diagnosed esophageal cancer cases occur in Asian countries, and two thirds of the world’s new cases of gallbladder cancer happen in this region. More strikingly, China alone contributes more than 50% of the world’s newly diagnosed liver and esophageal cancer cases, and 42% of newly diagnosed stomach cancer cases.

These Asia-prevalent cancers, compared to common tumor types such as breast, colon and lung cancer, have disappointing survival rates upon diagnosis at various stages of cancer. Attributing to this plight is the low number of approved anti-cancer drugs available to contain these life-threatening diseases (see Figure 1).

All aforementioned poses far-reaching challenges to Asia’s diverse health systems, especially illustrated by the disequilibrium of supply and demand of clinical services and anti-cancer drugs, escalating health expenditures along with rising healthcare expectations among Asia’s expanding middle income population.

There are many ways to address these devastating challenges, with the most forward-looking solution being the inception of molecular characterization and the introduction of cancer molecular diagnostics in the era of precision medicine.

Multiplex molecular diagnostics help improve clinical utility, drug development, and most importantly, it’s cost-effective

To be clear at the outset, molecular characterization in this article refers to DNA mutations, gene translocations and protein over-expression. Through adequate multiplex diagnostics such as next generation sequencing (NGS),2 molecular characterization is able to capture complex genomic changes,3 which is predominantly and uniquely present in cancer tissues.

As we know, the development of cancer in most cases may involve more than one gene that leads to overgrowth and proliferation of cancer cells. Using the conventional diagnostics to test multiple genes is not practical, as it requires a substantial amount of specimen, prolonged turnaround time and is costly.

What makes multiplex molecular diagnostics so powerful in delivering precision cancer therapy is attributed by comprehensive genomic profiling (CGP) and its underlying bio- and medical informatics. CGP enables physicians to select the most suitable treatment and find more treatment options based on each patient’s genomic characteristics in the hope to increase clinical response rates from 30 percent (the “imprecision” or conventional strategy) to more than double (see Figure 2).

In practice, multiplex molecular diagnostics has shown its promise in three manners. First, the clinical utility of using molecular profiling to guide treatment of advanced cancer patients was demonstrated by Stockley et al,4 in which patients were stratified according to their genomic profile using molecular diagnostics. Analyzing an impressive 1,640 cases, the percentage of patients who achieved tumor shrinkage doubled when prescribed treatments were matched to their genomic profile (32 per cent vs 62 per cent, see Figure 3). Hence, cancer molecular diagnostics does offer the chance to optimize drug effectiveness and safety.5

Second, the quest for molecular information has substantially emerged in drug development. An environmental scan in 2016 identified 15 therapeutics requiring molecular tests, most of them in oncology, and 39 anticipated drugs in development linked to 14 different molecular tests.6

Third, using multiplex molecular diagnostics for treatment selection is cost-effective. A recent economic model presented at the American Society of Clinical Oncology 2018 Annual Meeting compared different types of genetic tests for newly diagnosed metastatic non-small cell lung cancer. Calculated for a hypothetical 1 million health insurance members in the US, the study found that using NGS to analyze all known lung cancer-related genes at the time of diagnosis was more cost-effective and faster than testing one or a limited number of genes at a time. Strikingly, for commercial health plans, NGS would save a total of $127,402 compared to sequential and $250,842 compared to panel testing7 (see Table 1).

In summary, the advancements in molecular diagnostics are highly promising to address the unmet needs in cancer care and to deliver its promises to Asian cancer patients. However, there are still major hurdles present today that cripple the access to cancer molecular diagnostics in Asia.

Hurdles in the access to cancer molecular diagnostics in Asia

There are three major interdependent hurdles that need to be addressed if cancer molecular diagnostics is here to stay, and for it to realize its full potential in Asia. These are: (1) awareness of cancer molecular diagnostics, (2) availability of approved drugs and (3) affordability of genomic profiling.

Awareness. In general, cancer specialists, either internists or surgeons, are not so aware or not keeping abreast of the role cancer molecular diagnostics platforms can play in the patient journey. Most would arguably be lukewarm in learning the differences and practicality in the complex technical features of various diagnostics, not to mention the clinical applications. Lack of awareness of cancer diagnostics among clinicians may curb the diffusion and adoption of state-of-the-art genomic profiling techniques for those patients who may benefit from it. However, in the era of rising consumer expectations, patients, as well as their family members, will be more proactive and participative in requiring the best possible treatment they shall receive8 as long as drugs and diagnostics are available.

Availability. Access to new anti-cancer drugs has long been an issue of concern in Asia. Strikingly, less than half of the targeted therapies approved between 2010 and 2014 were available in Asian countries in 2015 (see Figure 4). Compared to developed countries where most targeted immunotherapies are readily available, only few of the emerging markets in Asia have registered these treatments. The situation has not improved much because, even when available through the regulatory review process, the national health systems’ priorities or public insurance programs eventually decline to reimburse innovative but pricey therapeutics. Ultimately, it all sums up to the fundamental question of socio-economic status, illustrated by the level of affordability in the region.

Affordability. Asia is a very cost-sensitive and elastic region. Undoubtedly, cost becomes a major determinant that facilitates or prohibits the dissemination of any healthcare technology. This is particularly true in Southeast Asia where annual health expenditure is around 550 USD per capita, on average. Indeed, in developing economies, such as the Philippines and Indonesia, where healthcare expenses are mainly from out-of-pocket, cancer patients may end up in great debt as they need to bear the treatment costs and other care related expenses, such as molecular diagnostics, personally. Hence, patients may choose not to undertake any additional diagnostics because they cannot afford the entire anti-cancer course that follows.9 Affordability of molecular diagnostics ultimately determines whether genomic profiling will only be reserved for the rich and the few.

What’s next

The consequences of not adopting molecular diagnostics in cancer care are serious: for patients, delayed diagnosis can make even the best treatments ineffective and a long series of diagnostic missteps can prove expensive; for doctors, delay and under-diagnosis of cancer can impede advances in genomic understanding of cancer and diagnostic trends.

Obviously, there is no quick fix for Asian countries to improve the access to next generation diagnostics. However, in our opinion, starting from a national reimbursement scheme may enable the unlocking of the complex hurdles so as to ease the financial burden of anti-cancer drugs, and eventually consider covering molecular diagnostic tests.

In other words, payers, such as national governments and private insurers, have to consider reimbursing or at least partially subsidizing diagnostic expenses through either social health insurance or publicly-supported cancer care platforms to better protect citizens from the costs associated with cancer diagnostics. By using adequate molecular characterization platforms, patient outcomes may be improved and costs reduced when cancer is diagnosed early and treated appropriately.

References:

  1. International Agency for Research on Cancer – World Health Organization. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. Available from: http://globocan.iarc.fr/Pages/fact_sheets_population.aspx
  2. NGS is a high throughput platform that generates massive sequencing data in a single run with minimal sample amount (e.g. 40-80 ng of DNA) required. With a short turnaround time of two weeks, this technique allows rapid and comprehensive genomic profiling that meets the clinical requirements for patients and doctors to tailor their treatment strategy. With just a fraction of precious samples, NGS can achieve an average sequencing depth of 1,000X to detect genetic alterations with high sensitivity.
  3. Cancer is caused by germline or somatic mutations in cancer-related genes. About 300-500 genes among the 20,000 human genes are related to cancer.
  4. Stockley TL et al. Molecular profiling of advanced solid tumors and patient outcomes with genotype-matched clinical trials: the Princess Margaret IMPACT/COMPACT trial. Genome Medicine (2016); 8: 109. Available from: https://genomemedicine.biomedcentral.com/track/pdf/10.1186/s13073-016-0364-2
  5. Slater J et al. The emergence of precision therapeutics: New challenges and opportunities for Canada’s health leaders. Healthcare Management Forum (2015); 28: S33-S39. Available from: http://journals.sagepub.com/doi/pdf/10.1177/0840470415604771
  6. Cowling T et al. Canadian Agency for Drugs and Technologies in Health Environmental Scan. Pharmaceuticals requiring companion diagnostics (2016); 57. Available from: https://www.cadth.ca/sites/default/files/pdf/ES0301_Drugs_with_cDx.pdf
  7. Pennell NA et al. Economic impact of next generation sequencing vs sequential single-gene testing modalities to detect genomic alterations in metastatic non-small cell lung cancer using a decision analytic model. Journal of Clinical Oncology (2018); 36 (suppl; abstr 9031). Available from: http://abstracts.asco.org/214/AbstView_214_223721.html
  8. Mnookin S. One of a kind. What do you do if your child has a condition that is new to science? The New Yorker (21 July 2014); P32. Available from: http://demystifyingmedicine.od.nih.gov/DM15/m4d21/reading01.pdf
  9. Barzi A et al. Comparative effectiveness of screening strategies for Lynch syndrome. Journal of the National Cancer Institute (2015); 107: djv005. Available from: https://academic.oup.com/jnci/article/107/4/djv005/894213

Dr Allen Lai is the senior vice president at ACT Genomics Singapore.


Dr Maarja-Liisa Nairismagi is the medical science liaison and project manager at ACT Genomics Singapore.

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EDITORS' CHOICE  
COLUMNS  

APBN Editorial Calendar 2018
January:
Obesity / Outlook for 2018
February:
Searching for the fountain of youth
March:
Women in Science - Making a difference
April:
Digestive health in the 21st century - Trust your guts
May:
Dental health - The root to good health
June:
Cancer - Therapies and strategies for better patient outcomes
July:
Water management - Technologies for biotech and pharmaceutical industries
August:
Regenerative technology - Meat of the future
September:
Doctor Robot - The digital healthcare revolution
October:
Bones / Breast cancer
November:
Liver health / Top science research nations & institutions
December:
AIDS / Breakthrough of the year/Emerging trends
Editorial calendar is subjected to changes.
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