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  • 15 to 20% of breast cancer patients suffer a type of the disease that could benefit from the drug Herceptin
  • Herceptin is very effective and normally administered for 12-months but it is expensive and can cause heart damage
  • New research has found that the treatment period for Herceptin could be reduced from 12-months to 6 without compromising outcomes
  • A 6-month course would reduce the cost of the drug, increase access and potentially reduce the number of patients suffering debilitating side effects
  • The research findings reignited broader concerns about the sustainability of cancer care and the competing interests of patients, producers and providers
  • Herceptin’s patents are expiring and biosimilars are entering the market which is expected to lower costs and increase access
 
After 20 years of the cancer drug Herceptin is less more?

Findings of a phase III clinical study funded by UK government grants and presented at the June 2018 meeting of the American Society of Clinical Oncology (ASCO) suggest that the time a patient needs to spend on Herceptin, (chemical name trastuzumab), a drug widely used to treat an aggressive form of breast cancer, could be halved from 12 to 6 months. This would save insurers, governments, healthcare providers and patients significant sums of money and possibly reduce the incidence of side effects, which can include heart problems.
 
In this Commentary
 
This Commentary: (i) summarizes the findings of the clinical study and some expert reactions to it and (ii) describes the different subtypes of breast cancer and the drug trastuzumab.  The Commentary also broaches a broader concern about the escalating costs of life-saving or life-extending cancer therapies, which show no sign of either slowing or reversing. According to ASCO, in the US, newly approved cancer drugs cost on average US$10,000 per month, with some costing as much as US$30,000 per month. This causes financial hardship for many American patients and their families. In the UK, which has a large devolved public healthcare system, cancer therapies are a postcode lottery because medicines that patients receive depend on whether their local healthcare provider can afford them. In emerging economies, where the prevalence of breast cancer is rising, only a privileged few breast cancer patients have access to trastuzumab. Notwithstanding, patients should gain some comfort from Herceptin’s patents expiring and biosimilar versions of trastuzumab entering the market, which is expected to make the drug cheaper and more accessible.  
 

Breast cancer and HER2

Breast cancer is a heterogenic disease and biomolecular changes in breast cancer involve the expression of genes. The disease is classified according to the 4 subtypes of genes expressed: (i) luminal A, which accounts for 51 to 61% of all breast cancer patients, (ii) luminal B, which accounts for 14 to 16%, (iii) basal-like, which accounts for 11-20% and (iv) the HER2 subtype, which accounts for 15 to 20% of all breast cancer patients and is the focus of this Commentary. Each subtype has different clinical features, different prognoses and different responses to therapies. HER2 protein overexpression is the result of amplification of the HER2 gene and is associated with aggressive tumour growth and consequent high rates of recurrence and mortality in patients. HER2-positive breast cancer is not inherited but is a somatic genetic mutation, which occurs after conception and therefore the new DNA does not enter the eggs or sperm.
 
Trastuzumab the first gene targeted drug
 
Trastuzumab was first approved by the US Food and Drug Administration (FDA) in 1998 and became the first FDA-approved therapeutic antibody targeted to a specific cancer-related molecular marker. The FDA recommended that the drug should be administered for 12 months. Robert Leonard, formerly Professor of Cancer Studies at Imperial College London, UK, and a consultant medical oncologist specialising in breast cancer at the BUPA Cromwell Hospital, the London Clinic and the London Oncology Clinic describes HER2 positive breast cancer and trastuzumab: see video below.  “We like to talk about targeted therapies since we’ve learnt more about the basic biology of cancer, which uses subtle techniques of investigation including biological and immunological profiling of cancers. We now have the ability for new molecules to target specific abnormalities in cancer cells and these can be effective in sublimating standard breast cancer treatments. A good example are Herceptin and Lapatinib, both of which target the HER2 pathway, which is a very important pathway in breast cancer,” says Leonard.
 
Trastuzumab and advanced breast cancer
Trastuzumab’s approval followed 4 randomized clinical studies involving more than 8,000 patients with stages II or III HER2-positive breast cancers. These showed that when trastuzumab was administered for a period of 12 months in combination with or after chemotherapy agents, it potentiated the efficacy of chemo- and immunotherapy; reduced the risk of breast cancer recurrence by approximately 50% and significantly improved survival. In 2000, trastuzumab's use for advanced breast cancer was approved in Europe and has since been approved in a number of countries outside Europe. In 2002 the UK government’s watchdog, the National Institute for Health and Clinical Excellence (NICE), endorsed the use of trastuzumab for advanced HER2 breast cancer.



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Trastuzumab and early stage breast cancer
Shortly afterwards, trastuzumab expanded its use to early stage HER2 breast cancer. Findings of 2 papers in the October 2005 edition of the New England Journal of Medicine (NEJM), suggested that following initial interventions, a 12-month course of trastuzumab in combination with other agents, could also be a lifesaver for those still in the early stages of breast cancer because it reduced the risk of recurrence and death of patients by 46% compared with chemotherapy alone. In this respect trastuzumab has been viewed as a possible “cure” for early stage breast cancer. Based on these findings, trastuzumab’s approval was extended for the treatment of early stage HER2 cancers. Commenting on the 2 studies in the same edition of the NEJM Gabriel Hortoboagyi, a breast cancer specialist from MD Anderson Cancer Center in Huston, USA, said, “the results reported in this issue of the Journal are not evolutionary but revolutionary. . . . . . trastuzumab and the two reports in this issue will completely alter our approach to the treatment of breast cancer.” In September 2013, a time-saving subcutaneous formulation of trastuzumab was approved in Europe, which can be administered in just 2 to 5 minutes, rather than the standard 30 to 90 minutes intravenously.
 
Was the 12 months treatment time a “guess”?
After regulatory approval in 1998 and following some subsequent clinical studies, a 12-month regimen for trastuzumab became the standard of care. Notwithstanding, some oncologists view the 12-month treatment period as a “guess”, and some smaller trials have questioned the duration of treatment.
 
Clinical study and the 2018 ASCO Meeting
 
The study presented at the 2018 ASCO meeting is the largest and most significant study to-date, which suggests that the treatment time for trastuzumab could be halved. The randomized clinical study followed 4,088 women with early-stage breast cancer across 152 sites in the UK for a median of more than 5 years: 2043 received trastuzumab for 6 months and 2045 received the drug for 12 months. The disease-free survival rate at 4 years was 89.4% with 6 months of therapy and 89.8% with 12 months of therapy. In addition, 4% of patients on the shorter treatment dropped out due to cardiac toxicity versus 8% of those treated for a year. Across both groups, cardiac function recovered within a few months following treatment with trastuzumab but patients in the 6-month group recovered more rapidly.

Helena Earl, Professor of Clinical Cancer Medicine at the University of Cambridge, UK and the study’s lead investigator is confident that the study will, “mark the first steps towards reduction of treatment duration for many women with HER2-positive breast cancer." According to Richard Schilsky, ASCO’s Chief Medical Officer, “There’s no reason to not immediately change practice. The findings are persuasive”.

 
Expert reaction to the study

Although oncologists view the study’s findings as “persuasive”, changing the length of treatment time for trastuzumab might not occur quickly. Generally, clinicians appear hesitant to immediately support a shorter duration of trastuzumab as a new standard of care. Some believe that since so few women have died or relapsed after being treated with trastuzumab, longer follow-up may be required to make sure the findings hold up before guidelines are changed. 

My guess is that people will continue to aim for a year of treatment' because of lingering concerns that longer use is better, as a smaller previous study suggested,” says Harold Burstein, a breast cancer expert at the Dana-Farber Cancer Institute in Boston, USA. However, Burstein is mindful that a shorter treatment regimen might increase access to trastuzumab for patients in emerging economies where the prevalence of breast cancer is increasing but where many women cannot afford a 12-month treatment course of the drug.  Other experts suggest that the study’s findings are significant for women who suffer the toxic effects of trastuzumab.

Jennifer Litton, a breast cancer specialist at MD Anderson Cancer Center points to another issue the ASCO study raises. She suggests the study’s findings show just how important it can be to study drugs that are already on the market. “It's really important that we continue to have public funding for clinical trials, so we can continue to ask all of these questions for our patients. Scaling back treatment whenever possible is important to patients,” says Litton.

Industry response
A spokesperson for Roche Genentech, Herceptin's developers, suggested that the ASCO study should be viewed along with several smaller studies, which conclude that the optimum duration for trastuzumab is 12 months. The goal of the treatment, “is to provide people with the best chance for a cure.” Courtney Aberbach, a spokesperson for Genentech, which was acquired by Roche, in March 2009 for US$$46.8bn, suggested that previous studies had not found that a shorter duration worked as well as the longer one. She said the 12-month course was still the only regimen approved for early-stage disease by the FDA and recommended by several international organizations that issue treatment guidelines.

The HERA Trial
Industry views are influenced by a clinical study sponsored by Roche in the expectation that the 12-month trastuzumab treatment period could be doubled. Referred to as the HERA trial, the study was conducted by France's Institut National du Cancer and reported at the 2012 meeting of the European Society for Medical Oncology (ESMO). HERA was an international multi-centre, phase III randomized study involving 5,102 women with early HER2-positive breast cancer. After finishing primary therapy with surgery, chemotherapy and radiotherapy, they were randomly assigned to trastuzumab therapy every 3 weeks for 1 year, 2 years or observation.
 
In April 2012, when the study’s findings were presented at the ESMO meeting, the overall survival rate of the 24-month treatment cohort versus the 12-month cohort was comparable. The principal conclusion of the study was that 12-month treatment remains the standard of care for HER2 positive early breast cancer patients. Results also suggested that shortening treatment of trastuzumab to 6 months may offer a worse result than a 12-month course of treatment. While the study’s findings meant that Roche missed an opportunity to expand sales of trastuzumab on the back of a longer recommended treatment period, they were also a relief to the company, which had faced the risk of losing significant sales revenues from trastuzumab had a shorter treatment period turned out to be as effective as the current standard of 12-months.
 
Unsustainable of cancer care

Cancer treatment has always been expensive, but the costs of newer molecular targeted therapies, such as trastuzumab, have escalated, which significantly reduces access for a lot of breast cancer patients to efficacious drugs. According to a 2015 study by the US National Bureau of Economic Research, each year between 1995 and 2013 the prices of cancer drugs increased 10%. This finding led some health professionals to suggest that cancer therapies are becoming “unsustainable”. In England, NICE has come under intense criticism from patient groups for rejecting numerous cancer drugs for use on the NHS because they were not judged to be cost effective. The UK’s Cancer Drugs Fund, which was set up in 2011 to plug gaps in NHS funding for cancer drugs, overspent its allocated budget by 35% between 2013 and 2015. The debate of the rising cost of cancer therapies is exacerbated by the revenues generated by cancer drugs for big pharmaceutical companies. For example, in 2017 Roche-Genentech recorded annual sales of US$6.8bn for Herceptin alone, which some analysts suggested was driven partly by the duration of the treatment and partly by strong sales growth of the drug in Brazil and China.

When vast revenues from the sale of drugs are mentioned there is negative reaction directed at giant pharmaceutical companies. In their defence drug producers stress the vast costs of developing new drugs and the tenure of patents, which limit the time drug companies have to recoup R&D costs before copycats are introduced into the market. According to the most recent report from the Tufts Center for the Study of Drug Development, and published in the May 2016 edition of the Journal of Health Economics; the cost of developing a medicine from invention to pharmacy shelves is estimated to be some US$2.7bn. Patents protect drugs for 20 years after the initial invention. This exclusivity is designed to promote a balance between new drug innovation and greater public access to drugs, which result from copycat versions.  Notwithstanding, big pharmaceutical companies stress that it can take 8 to 12 years after invention to accumulate enough data to get a drug past the FDA.
 
Biosimilars

For 20 years now Roche-Genentech has benefited from its 90% market share of the HER2-positive global breast cancer market. Notwithstanding, the main EU patent for Herceptin expired in 2014 and is due to expire in the US in 2019. Already, the market has experienced the entry of biosimilar versions of trastuzumab, which are expected to be cheaper and therefore extend patient access to the drug. Biosimilars are not to be confused with generic drugs. Regulators require biosimilars to be “highly similar” to the “reference product” but not exact copies of the biologic medicine. Biologic medicines are comprised of large complex molecules, which may be composed of living material. Here we provide some examples of the biosimilar versions of trastuzumab, which are coming onto the market.
 
Trastuzumab biosimilars
 
In December 2017, a biosimilar version of trastuzumab was approved by the FDA and is marketed in the US as Ogivri. Approval of Ogivri was based on a review of evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data and other clinical safety and effectiveness data, which demonstrated that Ogivri is biosimilar to trastuzumab. In 2018, Merck Sharp and Dohme (MSD) launched Ontruzan, in the UK, which is Europe’s first biosimilar to Herceptin. Clinical studies have shown Ontruzan to be similar to trastuzumab in terms of its structure, biological activity and efficacy, safety and immunogenicity profile. Studies also showed that in early breast cancer, breast pathologic complete response rates were 51.7% with Ontruzant and 42% with Herceptin, while overall response rates were 96.3% and 91.2% respectively. Mylan and Biocon have launched a biosimilar version of trastuzumab called Canmab in India, and Celltrion, has launched Herzuma, another biosimilar version of trastuzumab in South Korea. According to Mark Verrill, head of the Department of Medical Oncology at the Newcastle upon Tyne Hospitals NHS Foundation TrustUK, “The launch of biosimilar trastuzumab provides a high-quality treatment alternative for patients, while offering significant potential savings for health providers and patients.”
 
Takeaways
 
The clinical study presented at the June 2018 meeting of ASCO suggested that the treatment time for trastuzumab could be reduced from 12 months to 6 without compromising outcomes. This would significantly reduce the cost of trastuzumab and thereby make the drug available to more breast cancer patients. Although the study’s findings are “persuasive” there is a reticence among clinicians to reduce the treatment time of trastuzumab. The ASCO study throws light on the challenges to reconcile the competing interests of patients, healthcare providers and drug companies. While pharmaceutical companies spend billions on R&D they are challenged to reconcile the demands of shareholders and society. Public funds for medical research, while important, are limited especially at a time of relatively slow economic growth and fiscal constraint. Given that there does not appear to be any credible suggestion to curtail the vast and escalating cost of cancer care more generally, the current situation, which incentivises giant pharmaceutical companies to invest in R&D with 20-year patents, appears to be a formula that will prevail for some time to come, and patients will have to wait significant lengths of time before they get access to biosimilars.  
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  • International study shows that while British cancer survival has improved over the past 20 years the UK’s cancer survival rates lag behind the European average in 9 out of 10 cancers
  • 10,000 cancer deaths could be prevented each year if the UK hit the European average
  • Analysis shows that some British cancer survival rates trail that of developing nations such as Jordan, Puerto Rico, Algeria and Ecuador
  • Since the inception of the NHS in 1948 policy makers and clinicians have viewed the problem as the NHS being under staffed and underfunded
  • But the answers to the cancer care challenge in the UK are not that straight forward
  • The world has changed and is changing while policy responses to challenges have remained static
 
UK cancer care lags that of other European nations: reasons and solutions
Part 1

 

This Commentary is in 2 parts
Part 1 focusses on cancer care in the UK, but much of its substance is relevant to other advanced nations with aging populations and large and escalating incidence rates and costs of cancer. Before drilling down into cancer care in Britain we briefly describe the etiology of cancer, the epidemiology of the condition as it relates to the UK and other wealthy nations, mention immunotherapy as indicative of evolving and significant new therapies, which give hope to cancer sufferers. We then describe the CONCORD-3 study reported in The Lancet in 2018. This is a highly regarded and significant international study, whose findings are widely recognised as the “gold standard” of comparative cancer care. It reports that although 5-year cancer survival rates (the internationally accepted indicator of cancer care) have improved in Britain over the past 2 decades, the UK is still trailing that of most large European countries. We conclude Part 1 with a brief description of UK initiatives to close its cancer-gap with other European countries.
 
Part 2, which will be published in 2 weeks, is an analysis of the cancer-gap between Britain and other European countries. We suggest that for decades, healthcare providers, policy makers and leading clinicians have suggested that the UK cancer-care gap is because of the lack of funding and the lack of healthcare professionals. Since the inception of the NHS in 1948 a policy mantra of “more” has taken root among policy makers, providers and clinicians: predominantly, “more money”, “more staff”, and “the government should do more”. We suggest that, over the lifetime of NHS England, a combination of Britain’s economic growth, its historical ties with Commonwealth countries and, since 1973, the reduction of barriers to the flow of labour between European countries, has given UK policy makers a convenient “get-out-of-jail-card” because they could always provide more money and more staff. Over the past 2 decades, this option has become less and less effective because of a combination of the slowdown of world economic growth, the rise of emerging economies such as India, and more recently Brexit.
 
We conclude with some thoughts about why a significant cancer care gap has opened between the UK and other European nations, and briefly describe some UK initiatives to close the gap. We suggest that the world has changed quicker than the thinking of policy makers and quicker than structural changes in the UK’s healthcare system. Improving cancer care in the Britain will require more than inertia projects. It will require more innovation, more long-term planning, more courage from policy makers, more focus on actual patients’ needs rather than what we are simply able to provide. Since 1948, the healthcare baton in the UK has been with an establishment comprised of policy makers, providers and leading clinicians. Over the past 70 years this establishment has become increasingly entrenched in past and narrow policy solutions. It has failed because the world has changed while It has remained static. It is time that the healthcare baton is passed to people with less self-interest at stake, who are less wedded to the past, and understand the new and rapidly evolving global healthcare ecosystem.

 
The UK’s cancer challenge

While British policy makers and health providers appear keen to stress that trends in the 5-year cancer survival rates (the internationally accepted measure for progress against cancer) have improved over the past 20 years, there is an element of “economy with the truth” in what they say. The UK is being left behind by significant advances in cancer survival rates in other nations. Treatment for 3.7m UK cancer patients diagnosed since 2000 is struggling to progress, especially for people diagnosed with brain, stomach and blood cancers. Further, your chances of dying after being diagnosed with prostate, pancreatic and lung cancer in Britain is significantly higher than in any other large European nation. This is according to CONCORD-3, the largest ever international cancer study reported in the January 2018 edition of the The Lancet.
 

The emperor of all maladies
 
Cancer is the uncontrolled proliferation of cells. In his 2010 Pulitzer Prize winning book, ‘The Emperor of All MaladiesSiddhartha Mukherjee, professor of oncology at Columbia University Medical School in New York describes cancer cells as, "bloated and grotesque, with a dilated nucleus and a thin rim of cytoplasm, the sign of a cell whose very soul has been co-opted to divide and to keep dividing with pathological, monomaniacal purpose." Cancer occurs when a cell starts to divide repeatedly, producing abnormal copies of itself, rather than dividing occasionally just to replace worn out cells. If the immune system fails to destroy these cells, they continue to reproduce and invade and destroy surrounding healthy tissue. A number of forces can trigger these cell divisions, such as certain chemicals (carcinogens), chronic inflammation, hormones, lack of exercise, obesity, radiation, smoking, and viruses. ‘The emperor of all maladies’ is not just one disease. There are over 200 different types of cancer, each with its own methods of diagnosis and treatment. Most cancers are named after the organ or type of cell in which they start: for example, cancer that begins in the breast is called breast cancer. Cancer sometimes begins in one part of the body and can spread to other parts of the body through the blood and lymph systems This process is known as metastasis.
 
A practitioners’ views

According to Whitfield Growdon, an oncological surgeon at the Massachusetts General Hospital and Professor of Obstetrics, Gynaecology and Reproductive Biology at the Harvard University Medical School, Cancer is a complicated set of events, which can happen in any cell in your body. Your body is comprised of tiny cells, which have the ability to grow, stop growing and to re-model, which is necessary to do all the functions that are required for living. But every cell in nature has the potential to lose control of its growth. It is this uncontrolled growth of an individual cell, which we call cancer. Cells can grow, they can spread, and if the cell growth is uncontrolled it can invade other tissues, which can lead to you losing the ability to perform vital functions that are required for your life,” see video below:
 
 
Epidemiology

There is scarcely a family in the developed world unaffected by cancer. But, this has not always been the case. Cancer only became a leading cause of death when we began to live long enough to get it. In 1911, the prevalence of cancer was low compared to what it is today. Then life expectancy in the UK was 51.5 and 52.2 years for males and females respectively. Similarly, in the US, at the beginning of the 20th century, life expectancy at birth was 47.3 years. Today, the median life expectancy in the UK is 81.6 and in the US 78.7.  Significantly, the age at diagnosis for prostate cancer today is 67 and 61 for breast cancer. Approximately 12% of the UK population are aged 70 and above and account for 50.2% of the total cancers registered in 2014. 87% of all cancers in the US are diagnosed in people over 50.
Late diagnoses
 
Every 2 minutes in Britain someone is diagnosed with cancer, and almost 50% of these are diagnosed at a late stage. Every year in the UK there are more than 360,000 new cancer cases, which equates to nearly 990 newly diagnosed cancers every day. Taking a closer look at the UK data, we notice that since the early 1990s, incidence rates for all cancers combined have increased by 12%. The increase is larger in females than males. Over the past decade, incidence rates for all cancers combined have increased by 7%, with a larger increase in females: 8% as opposed to 3% in males. Over the next 2 decades, incidence rates for all cancers combined in Britain are projected to rise by 2%. Incidence rates in the UK are lower than in most European nations in males, but higher in females.

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Incidence rates of specific cancers in the UK

In 2015, breast, prostate, lung and bowel cancers together account for some 53% of all new cancer cases in the UK. Over the past decade, thyroid and liver cancers have shown the fastest increases in incidence in both males and females.  Incidence rates of melanoma, small intestine, and kidney cancers have also increased markedly in males over the past 10 years. Over the same period, Incidence rates of kidney, melanoma, and head and neck cancers have also increased markedly in females. Despite the rise in incidence rates, in recent years mortality rates from cancer in England and Wales have fallen. Between 1994 and 2013, mortality rates from cancer for males and females fell by 30% and 22% respectively.
 
New therapies: immunotherapy/biologics
 
What gives hope to people living with cancer is partly new and innovative therapies. Over the past few decades immunotherapy, also called biological therapy, is an evolving treatment, which has become a significant part of the management of certain cancers. Immunotherapy is any form of treatment that uses the body's natural abilities that constitute the immune system to fight infection and disease or to protect the body from some of the side effects of treatment. This may be achieved either by stimulating your own immune system to attack cancer cells specifically, or by giving your immune system components to boost your body’s immune system in a general way. Immunotherapy works better for some types of cancer than for others. It is used by itself for some cancers, but for others it seems to work better when used with other types of therapy.

According to Hani Gabra, Professor of Medical Oncology at Imperial College, London, and Chief Physician Scientist and Head of the Oncology Discovery Unit at AstraZeneca, UK, “Biological therapies are treatments gaining importance globally as we progress with the management of cancer. Understanding the biology of cancer has enabled us to understand the targets that go wrong in those cancers. We have successfully used many treatments that hit directly those cancer targets in order to inhibit or “switch-off” the cancers. These biological therapies either can be useful on their own or more commonly, combined with standard treatments such as chemotherapy, surgery and radiotherapy.” See video below:

 
 
Why is the CONCORD-3 study significant?

CONCORD-3 reported in a 2018 edition of The Lancet is an international scientific collaboration designed to monitor trends in the survival of cancer patients throughout the world, and involves 600 investigators in over 300 institutions in 71 countries. The study compares the overall effectiveness of health systems to provide care for 18 cancer types, which collectively represent 75% of all cancers diagnosed worldwide. The study is specifically designed to: (i) monitor trends in the survival rates of cancer patients world-wide to 2014, (ii) inform national and global policy on cancer control, and (iii) enable a comparative evaluation of the effectiveness of health systems in providing cancer care. The study is the third of its kind and supports the over-arching goal of the 2013 World Cancer Declaration, to achieve “major reductions in premature deaths from cancer, and improvements in quality of life and cancer survival”.
 
CONCORD’s evidence base
 
The evidence base of the CONCORD-3 study is significant and is predicated upon the clinical records of 37.5m patients diagnosed with cancer between 2000 and 2014. Data are provided in over 4,700 data sets by 322 population-based cancer registries from 71 countries and territories; 47 of which provided data with 100% population coverage. The analysis is centralised, based upon tight protocols and standardised quality controls, and employs cutting-edge methods. The 71 participating countries and territories are home to a combined population of 4.9bn (UN figures for 2014). This represents 67% of the world's population (7.3bn). The 322 participating cancer registries contributed data on all cancer patients diagnosed among their combined resident populations of almost 1bn people (989m), which is 20% of the combined population of those countries. CONCORD-3 contributes to the evidence base for global policy on cancer management and control.
 
CONCORD-3 data base drives national and global policies on cancer control

Despite the care taken of the data management processes, no study is perfect, and It is reasonable to assume that a study the size of CONCORD-3 will have weaknesses. Notwithstanding, the study is “best in class” and its results are comparable within the limits of data quality. The international trends in cancer patient survival reported in the study reflect the comparative effectiveness of health systems in managing cancer patients. The findings of CONCORD-3 form part of the evidence that drives national and international policies on cancer control. For example, the International Atomic Energy Agency use the findings in its campaign to highlight global inequalities in cancer survival. The Organisation for Economic Co-operation and Development (OEDC) use the results of CONCORD as indicators of the quality of healthcare in 48 countries in its Health at a Glance publications, and the European Union use the findings in its Country Health Profiles for EU Member States.
 
Overall cancer survival is improving

Overall findings of the CONCORD-3 study suggest that the prospects for cancer patients are improving throughout the world and survival rates are increasing for some lethal cancers. Several cancers show significant increases in 5-year survival, including breast (80% to 86%), prostate (82% to 89%), rectum (55% to 63%) and colon (52% to 60%); reflecting better cancer management. Notwithstanding, there are significant differences in cancer outcomes between nations.
 
UK has worse cancer survival rates compared with other European nations

Despite the fact that increasingly more people are surviving cancer, British adult cancer patients continue to have worse survival rates after 5 years compared to the European average in 9 out of 10 cancers. Research comparing 29 countries shows survival rates in Sweden are almost 33% higher than in the UK. For ovarian cancer, which affects 7,400 British women each year, the UK comes 45th out of 59, with only 36.2% sufferers surviving 5 years. Some countries achieve nearly double this survival rate. When the largest 5 European countries - Germany, France, Britain, Italy and Spain - were compared for the 3 most common cancers, Britain came bottom for 2 of them. Britain’s survival rates were worse than the other 4 European nations for lung and prostate cancer, and second worst for breast cancer. With regard to pancreatic cancer British patients had just a 6.8% chance of survival, compared to 7.7% in Spain, 8.6% in France, 9.2% in Italy and 10.7% in Germany. This puts the UK 47th out of the 56 countries that had full data for this cancer. Studies suggest 10,000 deaths could be prevented each year if the UK were to keep up with the European average. The UK only exceeds the European average in melanoma. See table below.
 
 
Takeaways

Here we have introduced and described the findings of CONCORD-3, which suggests the UK lags significantly other European nations with regard to cancer survival rates.  This sets the scene for part 2 of this Commentary, which will briefly describe some of the UK’s cancer initiatives to reduce premature death from cancer and enhance the care of people living with the disorder. Much has been achieved and over the past 2 decades, cancer mortality rates in the UK have been significantly reduced. Notwithstanding, more innovative and effective policies, which address the actual needs of patients rather than provide “more money and more staff” will be required if the UK is to reduce the cancer-care gap.
view in full page
  • International study shows that while British cancer survival has improved over the past 20 years the UK’s cancer survival rates lag behind the European average in 9 out of 10 cancers
  • 10,000 cancer deaths could be prevented each year if the UK hit the European average
  • Analysis shows that some British cancer survival rates trail that of developing nations such as Jordan, Puerto Rico, Algeria and Ecuador
  • Since the inception of the NHS in 1948 policy makers and clinicians have viewed the problem as the NHS being under staffed and underfunded
  • But the answers to the cancer care challenge in the UK is not straightforward
  • The global healthcare ecosystem has changed and is continuing to change faster than national policy responses
  • The UK’s cancer care challenges require more innovation not just more reports, more money and more staff
  
UK cancer care lags that of other European nations: reasons and solutions
Part 2

Part 1 of this Commentary  described the CONCORD-3 study reported in the January 2018 edition of The Lancet, which suggested that although 5-year cancer survival rates (the internationally accepted indicator of cancer care) have improved in Britain over the past 2 decades, the UK lags behind most large European countries in cancer care.
 
This is part 2 of the Commentary, which begins by describing some of the UK’s initiatives over the past 20 years to improve cancer mortality rates, speed up diagnoses and enhance the quality of cancer care for people living with the disease. All arrive at similar conclusions: that UK cancer care strategies have reduced cancer mortality rates over time, but there is still more that can be done. They do not compare Britain’s cancer mortality rates with other European nations. Notwithstanding, there appears to be some consensus among leading clinicians and policy makers that the UK’s failure to close the cancer care gap with other European nations is because NHS England is underfunded and understaffed. While this explanation might provide part of the answer it does not tell the whole story. The answer might be less to do with extra funds and extra staff, and more to do with the fact that the global healthcare ecosystem has changed quicker than the thinking of UK policy makers and quicker than structural changes to NHS England. To the extent that this is the case, improving cancer care in Britain may not require more money and more staff, but more innovation and more focus on actual patients’ needs rather than on what policy makers can provide politically.
 
National cancer initiatives: resolving patients’ needs or perpetuating the status quo?
 
Over the past 20 years the UK government has commissioned a number of strategies, taskforces and reports all aimed at improving cancer diagnoses, treatments, and management, and enhancing the quality of life of people living with the disease and reducing premature deaths. In 2000, NHS England launched a National Cancer Plan, which was, “committed to addressing health inequalities through setting new national and local targets for the reduction of smoking rates, the setting of new targets for the reduction of waiting times, the establishment of national standards for cancer services, and investment in specialist palliative care, the expansion and development of the cancer workforce, cancer facilities, and cancer research.” This was followed in 2007 by the Cancer Reform Strategy, which was designed to build, “on the progress made since the publication of the NHS Cancer Plan in 2000, and sets a clear direction for cancer services for the next five years. It shows how by 2012 our cancer services can and should become among the best in the world.”

 
Independent cancer taskforce
 
In January 2015, an Independent Cancer Taskforce was launched by NHS England, “to develop a five-year action plan for cancer services that will improve survival rates and save thousands of lives.” The NHS established the taskforce on behalf of the Care Quality Commission, Health Education England, Monitor,  Public Health England and theTrust Development Authority. The taskforce was chaired by Harpal Kumar, then, CEO of Cancer Research UK, and was comprised of representatives from a cross section of the cancer and healthcare communities.

In July 2015, the Independent Cancer Taskforce published a report entitled: Achieving world-class cancer outcomes: a strategy for England 2015-2020. The report identified key elements of a world class cancer care system and suggested that this is what British cancer patients should expect and what NHS England should aim to provide by 2020. The strategy included, “effective prevention (so that people do not get cancer at all if possible); prompt and accurate diagnosis; informed choice and convenient care; access to the best effective treatments with minimal side effects; always knowing what is going on and why; holistic support; and the best possible quality of life, including at the end of life.” According to the report such a strategy would achieve world-class cancer outcomes and save 30,000 lives a year by 2020.

 
2nd National Cancer Strategy

Two months before the publication of the Taskforce’s report, in May 2015, the UK government launched a National Cancer Strategy. This was its second 5-year program to implement a world-class cancer strategy designed to increase the prevention of cancer, speed up its diagnosis, and improve the experience of people with the condition. It suggested that rapid progress had been made in a number of key and high-impact areas, and stated that, “if someone is diagnosed with cancer, they should be able to live for as long and as well as is possible, regardless of their background or where they live. They should be diagnosed early, so that the most effective treatments are available to them, and they should get the highest quality care and support from the moment cancer is suspected.”

Report of the National Cancer Transformational Board
 
In December 2016, a National Cancer Transformation Board, led by Cally Palmer, the Cancer Director for England, published a number of specific steps to improve cancer care, and reported that over the past decade, 5-year cancer survival rates in the UK have improved across all main cancers, and at the end of 2016, cancer survival rates in Britain were at a record high with 7,000 more people surviving cancer compared to 2013.
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Interim report of the 2nd National Cancer Strategy

In October 2017, NHS England published an interim report of its 2015 National Cancer Strategy, which suggested that, “Survival rates for cancer have never been higher, and overall patients report a very good experience of care. However, we know there is more we can do to ensure patients are diagnosed early and quickly and that early diagnosis has a major impact on survival. We also know that patients continue to experience variation in their access to care, and this needs to be addressed. Early diagnosis, fast diagnosis and equity of access to treatment and care are central to the ‘National Cancer Programme’ and the transformation of services we want to achieve by 2020-21.” According to an NHS spokesperson, “Figures show that cancer survival is now at an all-time high in England, as a result of better access to screening, funding for effective new treatments and diagnostics and continued action to reduce smoking.”
 
Why cancer mortality rates in Britain lag other European countries
 
If you look at similar European countries the proportion of GDP (Gross Domestic Product) the UK has spent on health in the last 10 to 15 years is low and has increased less than the others,” says Michael Coleman, Professor of Epidemiology and Vital Statistics at the London School of Hygiene & Tropical Medicine and co-author of the international cancer study reported in the March 2018 edition of The Lancet. UK healthcare spending fell from 8.8% of GDP in 2009 - when it averaged 10.1% in leading European countries - to 7.3% in 2014-15. “This difference between the likes of Germany and France is likely to explain some of what we are seeing,” says Coleman and he also suggests that, “The number of medical specialists who deal with these diseases [cancer] tends to be low compared to other similar countries,” [Our emphasis]. Let us examine the relative European healthcare spends and levels of staffing in NHS England.
 
Comparative GDP spends on healthcare

The OECD’s November 2016 Health at a Glance report suggests that in 2013 (the latest year for which data have been published) the UK spent 8.5% of its GDP on public and private healthcare. And, a 2016 report from the King’s Fund, a charity, suggests that projected spending on NHS England as a proportion of the UK’s GDP in 2020-21 is 6.6%, just 0.3% above what it was in 2000.
 
Challenges comparing healthcare spends

Notwithstanding, linking cancer mortality rates to the proportion of GDP nations spend on healthcare is not straightforward. This is partly because of, (i) different nations have different sources of healthcare funding, and (ii) a person’s purchasing power is different in different countries. Fluctuations in relative national economic growth make such comparisons over time and between nations challenging. According to The Health Foundation, a higher percentage of UKhealthcare spending is publicly funded compared to other European countries. For example, “In 2012, publicly funded spending accounted for 84.0% of UK healthcare spending. This is the third highest level in the EU-15 (average: 76.5%).  In 2012, UK public spending on healthcare was slightly higher than the EU-15 average of 7.6% of GDP”. Between 2008 and 2012 the average annual change in healthcare spending per person was lower for the UK than most EU-15 countries, which was largely the result of Greece, Ireland and Portugal making significant cuts to their healthcare spending. The rising prevalence of cancer and other chronic long-term diseases, is a significant driver of increased healthcare costs. According to OEDC data, UK spend on chronic lifetime conditions is similar to the European average. However, the UK spends less than other European countries on pharmaceuticals and out-of-pocket payments. Further, on average, UK patients spend less time in hospital and generally use fewer resources (measured in terms of staff and beds).
 
A 2017 paper published by the Nuffield Trust suggests that, when taking into consideration different sources of healthcare funding and purchasing power parity, the UK’s healthcare spend actually might be keeping up with that of other European nations.
 
NHS “dangerously” understaffed

Let us now consider staffing. In 2017, The Royal College of Emergency Medicine reported that primary and emergency care doctors, which are crucial for the early diagnosis of cancer, were experiencing significant recruitment and retention challenges. According to 2018 figures, NHS England has nearly 100,000 jobs unfilled, which include 35,000 nursing posts and 10,000 doctor vacancies.  The total vacancies represent 1 in 12 of all NHS posts, which is enough to staff about 10 large hospitals. Further, the high number of unfilled NHS posts coincides with 0.25m more people visiting A&E in the first quarter of 2018 than in the equivalent period in 2016. According to Saffron Cordery, the director of policy and strategy for NHS ProvidersThese figures show how the NHS has been pushed to the limit. Despite working at full stretch with around 100,000 vacancies and a real risk of staff burnout, and despite treating 6% more emergency patients, year on year in December (2017), trusts cannot close the gap between what they are being asked to deliver and the funding available”. A February 2018 finance report suggests that NHS England is heading for a £931m deficit in 2018 and is "dangerously" understaffed. This year-on-year deficit was revised to a projected £1.3bn shortfall, which is 88% worse than planned.
 
Reasons for shortages of health professionals

The NHS staffing challenges are aggravated by the fact that British trainee primary care doctors are dwindling, newly qualified doctors are moving abroad, and experienced doctors are retiring early. Over the lifetime of NHS England, the UK has trained significantly fewer healthcare professionals than it needed, and the supply of qualified young British people has consistently outstripped the number of places in medical schools and nurse training. According to data from the General Medical Council (GMC), between 2008 and 2014 an average of 2,852 certificates were issued annually to enable British doctors to work abroad. A 2015 British Medical Association (BMA) poll of 15,560 primary care doctors, found that 34% of respondents plan to retire early because of high stress levels, increasing workloads, and too little time with patients.  Further, it is estimated that 10% of doctors and 7% of nurses employed by NHS England are nationals of other European countries. The uncertainties of Brexit (a term for the potential departure of the UK from the EU) add to NHS’s recruitment and retention challenges of healthcare professionals. According to a 2017 Health Foundation Report, in 2016, more than 2,700 nurses left the NHS; an increase of 68% since 2014.
 
UK policy approach to healthcare shortages has not changed

Notwithstanding, NHS staff shortages are not new. In the 1960s, NHS hospitals in Britain introduced mass recruitment from Commonwealth countries, and this has influenced staffing policies ever since. Being able to recruit doctors and nurses from foreign countries provided NHS England with an “easy” solution to staff shortages. However, over the past 2 decades the global healthcare ecosystem has changed significantly, while UK healthcare staffing policies have not kept pace with the changes. Today, there is a substantial gap globally in the supply and demand of healthcare professionals. Countries such as India, which traditionally could be relied upon to provide healthcare professionals for NHS England, have changed and the pool of potential Indian recruits have shrunk. Over the past 2 decades, the Indian economy has improved and the nation has developed a number of world-class hospital groups such as Apollo, Fortis and Narayana Health, which offer internationally competitive terms and conditions to Indian doctors and nurses. Increasingly Indian hospitals retain more of the nation’s healthcare professionals, and indeed attract doctors working in the UK and the US to return. Further, NHS England has tended to be staffed on the basis of what successive governments can afford rather than what NHS patients’ actually need.
 
Challenges of planning healthcare needs

Although there is a significant shortage of healthcare professionals in NHS England, it is not altogether clear that, (i) significantly increasing the number of NHS health professionals in the short to medium term will be possible, and (ii) simply increasing staff numbers will improve cancer care. Over the past 2 decades, as technologies and demographics have changed, so the demands on cancer professionals have changed. It is not necessarily the case that the NHS has the right mix of staff with the right mix of skills to deal effectively with changing conditions.  Changing traditional roles rather than simply boosting numbers might contribute more to reducing cancer mortality rates and improving the quality of cancer care. Further, it seems reasonable to suggest that, with the aforementioned challenges, a greater proportion of the UK’s annual healthcare spend might be more effective were it directed at cancer prevention rather than “diagnosis and treatment”.
 
Preventing cancer
 
A substantial proportion of cancers can be prevented including cancers caused by tobacco use, heavy consumption of alcohol, and obesity. According to the World Cancer Research Fund about 20% of all cancers diagnosed in the developed world are caused by a combination of excess body weight, physical inactivity, excess alcohol consumption, poor nutrition, and tobacco use, and thus could be prevented. Certain cancers caused by infectious agents such as the human papilloma virus (HPV), hepatitis C, (HCV), and human immunodeficiency virus (HIV) can be prevented by human behavioural changes, vaccination or treatment of the infection. Further, many of the 5m skin cancer cases worldwide (16,000 in the UK), which are diagnosed annually could be prevented by protecting skin from excessive sun exposure and not using indoor tanning machines.
 
Cancer screening
 
Screening is known to reduce the mortality of cancers of the breast, colon, rectum, cervix, and lung. Screening can help colorectal and cervical cancers by allowing for the detection and removal of pre-cancerous lesions. Screening also provides an opportunity for detecting some cancers early when treatment is less expensive and more likely to be successful. Early diagnosis is an important factor in improving cancer outcomes. Currently, the UK offers 3 national screening programs for bowel, breast and cervical cancer. Notwithstanding, recent reports suggest that these programs are not being fully utilised. For example, in 2017 the percentage of women taking up invitations for breast cancer screening was at the lowest level in a decade, dropping to 71%. Over 1.2m women in the UK (25% of the eligible population) did not take up their invitation for cervical screening. Further, a heightened awareness of changes in certain parts of the body, such as the breast, skin, eyes and genitalia may also result in the early detection of cancer.
 
Reconciling bureaucracy with innovation
 
We have described how UK cancer strategies are determined from the top. Cancer care professionals conform to internationally accepted standard processes, which facilitate and reinforce control. ‘Control’ and ‘conformism’ are in the DNA of cancer healthcare professionals and provide the cultural norms of NHS cancer care programs. NHS managers ensure conformance to clinical procedures, medications, targets, budgets, and quality care standards. This describes a classic “bureaucracy”, which is the technology of control and conformism, and the 70-year old command and control structure of NHS England. While control, alignment, discipline and accountability are very important to cancer care programs, innovation is equally important. If NHS England’s cancer mortality rates are to be compatible with those of other European healthcare systems we will have to find a way to reconcile the benefits of bureaucracy - precision, consistency, and predictability - while making the architecture and culture of our cancer care programs more innovative and more compatible with the demands of rapidly evolving 21st century science and technology.
 
Takeaways

Cancer is a vexed and profoundly challenging disorder. As soon as you read about a breakthrough you have news that the cancer has outwitted the scientists, hence the name, “the emperor of all maladies”. Cancer care in the UK has improved, but still the majority of British cancer patients would faire significantly better in other European countries. When reflecting on the myriad of cancer strategies, reports, and taskforces over the past 2 decade you cannot help but think that NHS England suffers from an element of bureaucratic inertia: the inevitable tendency of the NHS to perpetuate its established procedures and modus operandi, even if they do not reduce cancer mortality rates to those experienced by other European nations. The UK policy debate to resolve this problem tends to be dominated by “more”: more money, more doctors, more nurses. Historically this has provided successive governments with a “get-out-of-jail-card” because circumstances meant that the NHS could always provide more. This is not the case today. The global healthcare ecosystem has changed quicker than UK cancer strategies and quicker than structural changes in the nation’s healthcare system. Improving cancer care in the UK will require more than inertia projects. It will require more innovation, more long-term planning, more courage from policy makers, more attention to actual patients’ needs rather than providing what is politically available. The UK healthcare establishment should be minded of Darwin who suggested that, “It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”
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