Monthly Archives: October 2014

Only one day for advanced breast cancer

Marc Beishon

Marc Beishon

As October draws to a close, and another awareness month for the breast cancer movement, there is some good news for those living with or supporting those with advanced or metastatic breast cancer. This year there has been more emphasis on advanced disease amid the sea of pink ribbons and fundraising campaigns, which have tended to focus on early and curative stages of breast cancer, leaving many women (and some men) isolated from both the advocacy and medical communities.

This is particularly so in the US, where the pink ribbon campaigns were first launched. For four years, there has been a national metastatic breast cancer awareness day (13 October this year), and it has now attracted attention. Several national media outlets have highlighted the issues facing those with advanced disease, such as the Chicago Tribune and SFGate and there was an item on the TV programme, Good Morning America. Australia’s Breast Cancer Network joined in this year for the first time, but under the name of secondary breast cancer awareness.

Women speak out

A patient's blog

A patient’s blog

Advocacy groups such as the Metastatic Breast
Cancer Network
and METAvivor have been instrumental in the US in raising the profile of
advanced disease, and women with metastatic disease are taking to blogs to write about their experiences and how they feel about the lack of interest from the wider community – for example here and here. They are not only powerful testimonies but also calls to action for progress for their incurable condition, not least just being heard.

mbc coverAgain in the US, industry and advocates have come together in the Metastatic Breast Cancer Alliance to report on the status of research on advanced breast cancer, the quality of life of patients, what information and support is available, and public awareness. Not least, they aim to find out much more about how many people have metastatic disease. Their report (left) just published with the support of the Avon Foundation, is probably the most comprehensive review so far of these issues – and the agenda for the work needed is challenging, to say the least.

New survey data in the US has also informed Pfizer’s Breast cancer: a story half told initiative – as the company says: “Many people know little to nothing about metastatic breast cancer.” It joins a similar initiative sponsored by Novartis, Here & Now, which launched in Europe last year.

The advocacy movement in the US is particularly vocal, but if it has struggled to be heard, imagine how difficult things are in many other countries. There is an urgent need for much more to be done globally across the spectrum of issues – standards of care, research, and support for those with metastatic and locally advanced breast cancer.

ABC guidelines out

abc2The latest updated international guidelines (right) that cover this spectrum from ABC, the Advanced Breast Cancer conference, aim to help fill the gaps by applying current knowledge to patient care. The conference, held by the European School of Oncology (ESO) and the European Society for Medical Oncology (ESMO), is the only global event that brings together health professionals, researchers and advocates to publish such guidelines, which have recently been published in The Breast and Annals of Oncology – the full paper is free to download via the ABC site.

Progress in treating advanced breast cancer remains frustratingly slow, and awareness, support, and research funding are still low. The ethos of the ABC conference is to build on the momentum from the latest initiatives and especially to unite experience and research at a global level, and we encourage all to download the guidelines and help spread the word.

abcinfo2

 

A new scientific discovery – the good journalist!

Peter McIntyre

Peter McIntyre

If the public is to understand the world of cancer research and treatment they need translators to turn scientific jargon into simple, clear and accurate information. And yes, they do exist. They are called journalists!

ESO supported 14 health journalists from TV, radio, newspapers, magazines, online publications and news agencies across Europe to attend the  ESMO 2014 Congress in Madrid in September.

A top line of experts came and talked to this group on precision medicine, the role of diagnostics, immunotherapy, the changing face of clinical trials and the implications for patient care. The journalists, only some of whom have science degrees, asked sharp questions: How many drugs make a real difference? How can we tell when researchers are over-promoting results?

ESMO 2014 congress Media Room

ESMO 2014 Congress Media Room

Reporting for a lay audience

Later they shared valuable insights into the challenges of reporting on cancer for a lay audience.

Rinke Van den Brink, a health editor for NOS News, the Netherlands national public broadcaster, has a mixed public of “University professors and people who have barely finished primary school.” He describes himself as “a simple journalist who learned to ask questions” and says that if he cannot explain the science in simple terms, it will probably not make it onto the news.

Maria Pineiro, health reporter on El Progreso the Spanish regional newspaper (with 150,000 readers a day) focuses on significant treatments, whether the health system will pay and the social consequences of having cancer, rather than about drugs the Spanish economy cannot afford. “I do not see the point of writing about something that my readers are not going to get.”

Anja Gorenc who reports on health for the Slovenia Press Agency (STA), says that most of the best stories do not come from press releases. “I communicate a lot with other people because I am a journalist. I talk about health problems with my friends, my relatives and that is how I get ideas.”

Emanuela Schweninger, health correspondent for Realitatea TV in Romania, points out that television demands emotional impact as well as expert information. “In Romania we have 50,000 patients who need radiotherapy and only 12 machines in all the country. So if I am a patient who needs radiotherapy now, I need to wait three or four months … and this is a tragedy.

“I love my job. For me to be health correspondent is part of my life….. My mum has cancer so I know exactly what it means and I try every day to help patients who need my help.”

All the journalists benefited from talking to experts at ESMO and many made new contacts with specialists from their own countries. KateTreshchikova, health correspondent for the Russian regional newspaper, Voronezh Messenger, said: “Together I think we can change the situation in our region with oncology.”

Keeping it real

However, they expressed caution about “breakthroughs”. Italian science writer, Marco Boscolo, said: “We have a social responsibility in that we don’t have to provide false hope for people.” And Maria Pineiro, delighted to have learned so much about emerging treatments, stressed the need for realism. “Everybody is trying so hard [but]…. I think we are quite far away from real new treatments that can make cancer a chronic disease which is the main goal I think of most oncologists and researchers.”

These journalists combine a drive to explain the science with a strong sense of humanity. Researchers, clinicians and other experts would do well to watch these short interviews to understand the challenges they face.

Please click on the faces to view each video
Anja Gorenc

Anja Gorenc

Emanuela Schweninger

Emanuela Schweninger

Kate Treshchikova

Kate Treshchikova

 

Marco Boscolo

Marco Boscolo

Maria Pineiro

Maria Pineiro

Maria Tcherneva

Maria Tcherneva

Rinke Van den Brinke

Rinke Van den Brinke

Sonia Ionescu

Sonia Ionescu

Speeding up global access to detection and care

 

Dr Rengaswamy Sankaranarayanan

Dr Rengaswamy Sankaranarayanan

Rengaswamy Sankaranarayanan, special advisor on cancer control and head of early detection and prevention at IARC (the WHO’s International Agency for Research on Cancer), Lyon, will lead the session on Access to effective and affordable treatments in middle- and low-income countries at the World Oncology Forum, Lugano, October 23–25. In this guest blogpost he talks about the policy recommendations he will be arguing for.

I’M LOOKING FORWARD to speaking at the World Oncology Forum about new healthcare financing models that are extending access to effective early diagnosis and treatment of cancer in many low- to- middle-income countries. I would like to see the Forum issue recommendations that can catalyse the pace of this transformation and deliver a very blunt message to governments and international development agencies.

Some success stories

The last few years have seen important progress in access to healthcare, particularly in middle-income countries. I would like to see this replicated in low-income countries.

Thailand, for instance, started introducing universal healthcare from 2002. Today, anyone living anywhere in Thailand, can access care seamlessly across public health services.

Initially under the Thai scheme, people were required to make a single, small copayment – 30 Baht or around $1 – the first time they see a healthcare professional for a particular complaint. That payment would cover the entire journey that follows, including diagnostic tests, treatments and follow-up. This co-payment was abolished in 2007, and universal health care became free for poor people.

Despite initial fears that the health system would collapse, it is working well. One important reason is that the government is investing a substantial amount of its GDP into healthcare. Another is that the “30-Baht” scheme mainly covers people from the very poorest rural communities – those employed by the government and the private sector have their own insurance systems.

Not only has it considerably improved access to healthcare in Thailand, it has also regulated the market, because the system will only pay for standard procedures. Since then, many other middle-income countries have implemented successful schemes to widen access to healthcare, including Turkey, India and Malaysia as well as many of the larger countries in Latin America, such as Mexico, Brazil, Colombia, Peru, Argentina and Chile.

Spreading the success: two recommendations

1. Cancer control must be a national responsibility

Countries like Thailand have shown it is possible through a variety of models to provide sustainable good-quality health services on a subsidised basis for a large proportion of people, while recovering healthcare costs from those who can afford it.

However, we also need to learn from our failures. In sub-Saharan Africa, for instance, health services have barely improved, there are no health financing systems, and access to healthcare has not improved at all.

I think one of the major reasons for this is the amount of external assistance they receive, which has blunted internal investment and internal drive and internal planning.

We need to make governments realise that healthcare is their own responsibility, and the systems and investments they have to make should be their own, and should come from their own national budgets. The way to do this is to substantially increase the GDP proportion that is contributed to healthcare from national budget.

So one message I would like to come out of the World Oncology Forum is that:
International organisations and funding agencies should insist that the countries they help must predominantly use national resources to develop and sustain their own national healthcare services.

 2. Cancer control needs a joined up approach

Another lesson we need to learn is that countries need to approach cancer control as a whole, linking prevention, early detection, treatment and palliative care. In Latin America, for instance, screening with the Pap smear was carried out for many many years, with very little impact on disease. Everyone blamed the poor cytology, but the bigger problem was that most women with the positive cytology never had a diagnosis made and never received treatment.

Governments and international agencies need to take a more comprehensive view across the entire spectrum of cancer control.

I think we have lessons to learn here from the comprehensive approach taken by the GAVI alliance, which has been very successful in terms of immunisation coverage and reducing child mortality. So another key message I would like to see coming out of the World Oncology Forum is:
We need to think in terms of a global alliance for cancer care continuum.

 Other key issues

Other key issues I will be asking the World Oncology Forum to consider include:

  • The urgent need to secure universal access to basic early diagnosis and treatment services
  • Opportunities for working within the wider efforts to tackle “non-communicable diseases”
  • Reversing the worrying trend towards adopting expensive and unnecessary imaging investigations, very expensive, very high-tech radiotherapy equipment and techniques, and expensive chemotherapy regimens and targeted drugs whose additional benefit has not been well demonstrated.

I look forward to the discussion

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Turning targets into effective treatments. My three questions for the World Oncology Forum

 

Paul Workman

Paul Workman

This week 50 experts from across the globe involved in researching, developing, evaluating and delivering new therapies will meet to develop consensus recommendations on who needs to do what to speed the development of effective treatments. The meeting is one of a series of World Oncology Forum summits organised by ESO in collaboration with The Lancet.  

In this guest blogpost, Paul Workman, interim CEO of The Institute of Cancer Research, London, talks about the three questions he will be posing in his opening keynote speech.

AS SOMEONE WHO has spent a career in cancer drug discovery and development, in academic, biotech and big pharma settings, I find it very frustrating that we still lack the treatments we need to effectively control or cure many cancers.

So I welcome the opportunity to give the opening presentation at WOF 2014, and to ask questions about what has to happen to translate the tremendous insight and knowledge we now have about the genetics and biology of cancer into effective treatments.

I intend to open on an optimistic note.

The success of the human genome project and its application to oncology has led over the past decade to an extraordinary increase in our understanding of the causation of cancer, and has opened up a new, ‘personalised’ approach to treating cancer.

There is a feeling of positivity among cancer researchers which I certainly share. Genetics and biology are being laid open, and ideas about rational therapies are still pouring out of labs.

It’s true that, while some of the new personalised therapies have been very successful, the overall impact so far has been disappointing. But an important point I will be stressing is that we do understand what the limitations are – and based on this we can now devise scientifically rational ways forward to move us to the next level.

We now know that cancers are able to develop resistance to molecularly targeted drug treatments – just as they did to the previous generation of cytotoxic drugs. This is because cancer cells evolve over time through a sort of Darwinian ‘survival of the nastiest’.

Such evolution leads to the high level of genetic and biological variation of cancer cells within a given patient. Even worse, the treatments given can themselves act as a ‘selective pressure’ to drive further variation and resistance.

So the task ahead is ideally to design therapies that will block cancer evolution. One class of drugs that does this that we at the ICR have been heavily involved in developing – HSP90 inhibitors – are now in clinical trial. We need to find more targets of this type, for example those in epigenetic regulatory pathways.

Another important approach to overcome evolution and resistance is to develop drug combinations that can hit, for example, several different cancer targets or other alterations at the same time – a strategy which has worked well in controlling HIV.

But this is where we come up against a problem. Because, out of the 500 genes or so we have discovered that are responsible for causing cancer, we’ve only got drugs that will work against about 5% of them.

We still haven’t got any drugs that work, for instance, on RAS or on MYC or p53 – three of the big genes responsible for causing cancer. So we’re trying to find effective combinations when we have no drugs for 95% of genes that may be involved in resistance. There is a huge amount of work still to do in this key area.

Question 1
So a key question I will be posing at the World Oncology Forum will be: how do we speed up the development of innovative drugs against more of these new cancer targets?

Part of the answer to this problem involves the technical challenges to find drugs for the less ‘druggable’ targets. But in fact there is another more systematic problem which lies in the ‘ecosystem’ that governs the way new therapies are discovered, developed, brought to market and paid for. It clearly isn’t functioning as well as it should for developing personalised cancer therapies.

Most companies are working on a relatively small number of targets, maybe 20 or 30. They all tend to invest in the same group of targets and often they prefer trying to develop a slightly better version of a drug that is already out there rather than going for a new target.

Taking a higher-risk, more innovative approach and working on currently undrugged targets, rather than developing ‘me-too’ drugs, is much more likely to deliver the sort of step changes in survival that we all want to see.

The risk-aversion that predominates in the pharma industry is understandable, from their point of view. They know that historically only 5–10% of drugs that enter phase I show enough activity to be approved, so they want to be very sure about the targets they work on.

But that thinking creates an innovation gap, or what we call rather more dramatically the ‘valley of death’. There is a gap – in fact a chasm –  between early-stage research with real clinical implications, like the identification of a new target gene, or the discovery of a an early prototype drug candidate, and it being taken forward by companies to the point where a treatment can be trialled in patients.

Then there’s the problem that new drugs are being tested in settings where they are least likely to show a benefit, as single treatments given in late-stage disease which has already become drug resistant.

Even though we now have predictive biomarkers to select responsive patients, the benefit in heavily treated drug-resistant patients can be relatively small, which means that it takes more patients and a longer time to demonstrate in a clinical trial. This pushes up costs, which then means that bodies like NICE in the UK and its equivalents elsewhere may refuse to fund the drugs because they aren’t deemed sufficient value for money.

This is not helped by companies continuing to seek the maximum cost the market will bear. And once a drug has been turned down it becomes very difficult to find out what it might be capable of when used either earlier in the disease or in combination with other drugs. So great opportunities will be lost.

Question 2
So the second question I will be asking is, how can we incentivise the ecosystem to be more innovative in research and development?

I think the key to progress is all about decreasing risk aversion. Until now, the pharmaceutical industry has preferred to stick to tried and tested ways of discovering drugs and of steering them through the regulatory process – even though there may be strong scientific grounds for doing things differently when we’re dealing with rationally designed, targeted therapies and especially facing the challenge of cancer evolution and drug resistance.

It’s easy but fruitless to get into the blame game here. Pharmaceutical companies are not charities and they have a responsibility to their shareholders. Bodies like NICE have a responsibility to ensure health spending delivers value for money and regulators need to be convinced of the medical merits and safety of new therapies.

The question is how to find a way forward that works better for everybody.

If we accept that risk aversion is a big part of the problem – an assumption that is backed up by many conversations I have had and by my own experience in the industry – we have to find ways to bridge the innovation gap.

One way is to do more of the early high-risk drug discovery and development in the academic sphere, and in collaborations with Government, charities and industry.

Some organisations, such as Cancer Research UK and the National Institutes for Health in the US, are already pushing for this approach. They are beginning to provide ‘valley of death’-type funding to academic groups, including mine here at the ICR and MD Anderson and others, to help them get involved in early-stage, high-risk, innovative drug discovery and development. That can decrease the risk to industry in progressing a new approach.

I think this approach will really help, as exemplified by the breakthrough drug abiraterone that we discovered at the ICR and which was then subsequently licensed to industry and approved in late-stage prostate cancer.

We should be aware though that risk-aversion is not restricted to industry. There are many pressures at work in the academic sector – including hyper-competition, difficulties in accessing grant funding, and a preference for funding ‘safe’ rather than highly innovative approaches.

We also have to face tough questions about excessive requirements for publication which can actually slow progress and reduce efficiency. And conversely there are worries about the inability to replicate many academic discoveries in basic research which can then misinform choices about the best therapeutic targets to work on.

Question 3
So the final questions I will be pushing very hard at the end of my presentation will be: How do we de-risk innovative drug development for companies? Where will the high-risk work be done? Who will fund it? And what should we expect from companies and academia?

It is going to require concerted efforts from all parts of the ecosystem to overcome the challenges we face to overcome cancer evolution and drug resistance. We need to work together as a community to find win-win solutions.

I’m looking forward to the discussions at the Forum and believe they will help move us in the right direction.

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Heads up: it may be best to do nothing

Simon Crompton

Simon Crompton

 

It’s always strange emerging from the single-mindedness of a conference to breathe the outside world’s unconcerned air. I doubt there was a person attending the British Medical Journal’s recent “Preventing Overdiagnosis” conference in Oxford who didn’t come away with the sense that overdiagnosis and its consequences is one of the biggest challenges facing health providers globally.

 

But beyond the concern of a handful of international experts – many of whom were gathered in Oxford – awareness and concern among the international cancer community seems low. Yes, most of us know that there are risks as well as benefits to breast cancer screening, and that PSA testing for prostate cancer can lead to unnecessary tests and treatment. But does that result in changes to practice? Does every one of us need to sit up and listen a bit more?

The papers presented at the conference certainly suggested “yes”. As keynote speaker Ilona Heath, a former President of the Royal College of General Practitioners, said: “Susan Sontag’s kingdom of the well is being absorbed into the kingdom of the sick, and clinicians and health services are busy ushering people across this important border in ever-increasing numbers. The costs, personal, social and economic, are enormous.”

The issue of overdiagnosis doesn’t just hover over breast cancer and prostate cancer.

The conference heard evidence that it is an issue in melanoma. An analysis of data by America’s National Cancer Institute, presented at the conference, showed that melanoma incidence has been increasing since 1975 while mortality has remained stable, strongly suggesting overdiagnosis.

Or take ovarian cancer. The conference heard about concerns that improved testing with blood tests and ultrasound are leading to increased detection of borderline ovarian tumours that might never present clinically in the lifetime of a woman.

Or thyroid cancer. A population-based study of thyroid cancer patients in Ontario, Canada between 2000 and 2008 shows that this relatively benign cancer is increasing at an “epidemic” rate. The increase seems to be confined to more affluent areas, and closely related to the availability of diagnostic ultrasound.

The suggestion is that, without sophisticated diagnostic techniques, large numbers of people with these diseases would have died of something else without even knowing they had cancer. They might have avoided distressing decisions, painful tests, potentially disabling treatments.

Such interpretations of data can prove controversial. Some evidence is strong, some is preliminary to say the least. But it undoubtedly opens up important questions for all those involved in the detection and treatment of cancers. It asks us to look up from a heads-down determination to track down and destroy cancer, and question whether sometimes – quite often – doing nothing is the best course.

It’s not an easy thing to do. Cancer World will be exploring the issues in its next three editions.

An essential cancer medicines list for Europe

piccart1

Martine Piccart

Patients are still waiting to feel real benefit from the rapid advances in knowledge and technologyseen over the past decade. This October, 50 experts from across the globe involved in researching, developing, evaluating and delivering new therapies will meet to develop consensus recommendation on who needs to do what tospeed the development of effective treatments. The meeting is one of a series of World Oncology Forum summits organised by ESO in collaboration with the Lancet.


How can we improve access to important new cancer therapies? Martine Piccart – president of ECCO and past-president of ESMO, argues the case for a WHO-style essential drugs list for Europe.

WHEN I BECAME PRESIDENT OF ESMO (European Society for Medical Oncology) in 2012, I had on my agenda to visit countries of eastern Europe, because I was shocked by statistics indicating that even inside Europe there are significant differences in cancer outcomes between the western and eastern parts.

Of course there are huge discrepancies between Europe and Africa, for instance, but that this exists inside Europe came as a shock, so I decided to travel to the countries and talk to the oncologists there.

I will be talking at WOF about what I learned from them about their efforts to improve access to new therapies, and how that prompted ESMO to develop a rating scale to evaluate the magnitude of benefit of new anti-cancer drugs for solid tumours.

Which would I choose?

The idea is to help oncologists focus their lobbying efforts on the most important therapies, and also to strengthen their bargaining position, because they can show that the therapies they are asking for are considered to be very important by the wider medical oncology community.

It’s taken us more than a year to come up with something that we are beginning to be happy with. And we’re now awaiting input from patient organisations about rating impact on their quality of life.

It’s a first attempt at getting a community of oncologists to look at all the very expensive drugs that we have seen in development in the last 10 years and really asking the question: if I have to choose only a few, which ones am I going to choose.

Potential dangers

As I will explain, this was an interesting exercise. When you start something like that you think it is going to be easy, but then you discover that it is actually incredibly complicated and there are potential dangers. For instance, we don’t want it to be used by governments in an aggressive way, to decide that they are only going to pay for one or two top-scoring drugs and never for the others.

What I hope to present at WOF is the reasoning behind the development of the scale, and how we went about it, and why we think it will be important. And I’m looking forward to the discussion.

Convincing governments

More generally, I hope that WOF won’t just look at what needs to be done, but also how to convince governments and politicians to take the necessary action.

We need to be able to show them how outcomes for citizens in their country compare with what is being achieved in other parts of Europe, to bring home the consequences of lack of access to the right treatments – and this is not just about new drugs but also the basics of high-quality surgery and radiotherapy. I think this kind of language is more powerful for politicians than simply going to them and saying we need money and we need new innovative treatments

These sorts of comparisons require high-quality cancer registries with homogenous cancer data – something I was shocked to find out still doesn’t exist in many European countries. So I think more support for high quality registries must be one of the messages from this WOF.

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