Category Archives: WOF

We say “epidemic”, they say “breakthrough”: reframing the global cancer debate

anna portrait  picThe World Economic Forum, with its mission of “improving the state of the world through public–private cooperation” is where leading international figures from politics, business and civic society meet for informal discussions about the big global threats and opportunities of the day.

Getting cancer onto the Davos 2015 agenda was therefore a milestone, for which much credit should go to Franco Cavalli, a leading medical oncologist who chairs the World Oncology Forum and is a former president of the Union for International Cancer Control.

It should have been a great opportunity to engage global decision makers in discussions that have taken place within the cancer community about developing a response to the relentless global rise in cancer incidence, which is now the biggest cause of death along with cardiovascular disease.

However, while Davos did table sessions on cancer, they were not designed to discuss the strategic policy response the cancer community is calling for, and Cavalli, who had a seat at the table, came away with mixed feelings about what had been achieved.

Framing the debate

Last September, Cavalli was invited to participate in a pre-Davos panel on the topic Cancer: the Next Global Epidemic? to see if this would be suitable for inclusion on the full agenda. Alongside him were Chris Wild, Director of the WHO International Agency for Research on Cancer, Aaron Motsoaledi, the South African Health Minister, and Helmy Eltoukhy, a “technology pioneer” developing liquid cancer biopsies.

Early feedback was positive – cancer control seemed to have secured its place. However, when confirmation came at the end of December 2014, the focus had radically changed.

Any ambition for global action to support governments to sustainably expand access to early detection, treatment and care, had gone missing.

In its place were two sessions that focused on medical breakthroughs.

One of these, Cancer: Pathways to a Cure, framed the question as: “What breakthroughs in prevention and therapy offer a glimpse of a cancer-free future?

The other, titled A New Era in the Fight against Cancer, asked: “How will breakthroughs in specialized care and immunotherapy transform the future of cancer treatment?”

As Cavalli explains in the forthcoming issue of Cancer World, it proved hard to focus the discussion on what will make most difference to the 12 million people who develop cancer each year. Leading figures from research and the biomedical industry were keener to talk about their achievements, hopes and ambitions than to question the real-world impact of their work.

“It was a very difficult environment to present what we want to achieve,” said Cavalli.

There was an opportunity to discuss a possible policy response in a third session, the Globalization of Chronic Disease, but here the focus was entirely on promoting healthy environments and lifestyles, which doesn’t address the needs of people who develop cancers, many of which are not preventable.

Whose problem?

It is interesting to contrast the technological framing of the cancer sessions, with sessions on infectious diseases, which carried titles like “Confronting the Challenge of Catastrophic Outbreaks” and “Pandemics: Whose Problem?

The words indicate crisis, urgency, action, and a global responsibility – the responsibility world leaders previously accepted in setting up the Global Fund to Fight AIDS, Tuberculosis and Malaria, which has transformed access to information, affordable treatment and care.

As Cavalli argues in the forthcoming article, many leading political figures want a similar coordinated global initiative to tackle cancer, but their voices are not yet heard loudly enough.

His message to Davos? “We’ll be back!”

WOF @ Davos: reigniting the ambitions of the Paris Charter Against Cancer

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Martine Piccart, President of the European CanCer Organisation, ECCO

Cancer – the search for medical breakthroughs and responding to global needs – will this year feature for the first time ever on the agenda of the World Economic Forum in Davos.  ESO’s Franco Cavalli will be attending both sessions to promote calls from the World Oncology Forum for bold action to massively extend access to cancer detection, treatment and care, and improve the ‘ecosystem’ for developing and evaluating new therapies. In this guest blogpost, Martine Piccart, President of ECCO,  traces the spirit of the World Oncology Forum back to the Paris Charter Against Cancer, and talks about what she would like to come out of the sessions at Davos.

 

 

In 2000, President Jacques Chirac signed the “Charter against Cancer” in front of 200 cancer specialists from all around the world. This landmark event, initiated by Professor David Khayat, stimulated many countries to put in place their “national” cancer plans. Unfortunately, and yet predictably, this collective enthusiasm to seriously address a major threat to the wellbeing of citizens of the earth not only did not reach all countries but progressively died down.

The European School of Oncology revived this crucial movement when it initiated the World Oncology Forum under the chairmanship of Dr Franco Cavalli.  This initiative has again united leading cancer experts from different disciplines and different parts of the world to discuss the greatest challenges of the fight against cancer in the 21 century and prioritise possible solutions to an improved control of the “cancer epidemic”.

ECCO is engaged in similar strategic thinking that builds on its unique and very broad multidisciplinary platform to find more efficient ways to treat and care for cancer patients.

These efforts are critical in a world which is shockingly fragmented in the availability of essential cancer-fighting tools and resources and most importantly:

  • Well-developed cancer registries – too many countries still lack these and, as a result, are unable to monitor the advance of the cancer epidemic and the variable impact of cancer prevention measures or cancer therapies.
  • Adequate radiotherapy equipment (which is even non-existent in some parts of our supposedly modern world).
  • Access to cancer drugs – it is unacceptable to see problems with access to old but effective drugs which no longer generate a “profit” and at the same time witness the growth of a “two-level” patient care reality where only a minority of patients are able to receive the most innovative but very expensive targeted anticancer drugs.  There is a need for prioritization here, as not all these “innovative” drugs have been shown to deliver clinically meaningful benefits.

A revised partnership model involving academia, industry and governments is urgently needed as it will generate a healthier context with shared risks in the fascinating but difficult translation of basic science discoveries into improved and more personalized patient management.  I hope the spotlight on cancer at the World Economic Forum will accelerate the creation of just such a partnership model.

Davos: another milestone in global efforts to control cancer

anna portrait  picWorld leaders from governments, industry and civic society will gather in Davos next week to discuss how to respond to some of the most pressing issues facing the world today.

It is the annual meeting of the World Economic Forum, and this year the question of how to stem the rising tide of suffering and death from cancer will be on the agenda for the first time.

Two sessions are scheduled.

The first is an interactive dinner session on the Friday evening (Jan 23rd), titled: Cancer, Pathway to a Cure – What are the breakthroughs in cancer prevention and therapy?

This session offers an opportunity to ask questions about whether the research, development and regulatory “ecosystem” that we are relying on to deliver a cure for cancer is really fit for purpose. Where is the current succession of therapies – many using similar approaches to deliver incremental benefit at ever higher costs – really taking us? How can we reconfigure the business model to promote more innovative, ambitious approaches that can overcome the problem of drug resistance?

The second is a working session on the Saturday morning (Jan 24th), titled: Globalisation of Non-Communicable Diseases.

With governments across the world already committed to reducing preventable deaths from non-communicable diseases including cancer by 25% by 2025 (65th World Health Assembly, 2012), this session offers a welcome opportunity to put on the table the bold actions that must be taken at national and international level if governments are to have any chance of delivering on the commitments they made.

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Doubtless there will be many Davos participants who will bring their own agendas to the cancer sessions. Among them will be Franco Cavalli, chair of the World Oncology Forum – a gathering of leading cancer researchers, clinicians, and policy makers, convened by ESO in 2012 and 2014, in collaboration with The Lancet, that has already spelt out the bold actions that are urgently needed at national and international level to turn the tide on cancer.

These actions are defined in the Stop Cancer Now! appeal and two more detailed appeals, which fit neatly in with the two Davos sessions, on “Speed up progress towards a cure”, and “Treat the treatable”. Cavalli, who played a major role in getting cancer onto the Davos agenda, will be arguing strongly for these policies at the two cancer sessions.

Davos is traditionally important as a forum where constructive conversations can take place between specialists – eg from the world of cancer – who have a deep understanding of a particular problem, and people who have the power and responsibility to take the action required to find solutions.

This year, it is an opportunity to get the message across to world leaders that “business as usual” is not an option in the face of a cancer epidemic that is costing the world $2 trillion each year, and to begin to turn the policies that the cancer community has been calling for into actionable items on the agendas that matter.

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Bold policies for progress north and south

anna portrait  picWorking in silos has long been a problem within the cancer community, as people engaged in increasingly specialised fields struggle to remain aware of the bigger picture. So it can be important, on occasion, to bring the different constituents together around a single agenda.

One might have wondered, however, whether the World Oncology Forum, which gathered almost two months ago in Lugano, Switzerland, might not have been a little over-ambitious in setting an agenda that focused on two topics that are poles apart in almost every respect, including the geographical.

The first of these, fixing the ‘broken model’ of new drug development, is a priority issue for the northern hemisphere. The second, addressing unmet need for the most rudimentary detection, treatment and palliative care, is the priority in the South. The opportunity to explore these challenges and the associated policy implications, within a single gathering, however, turned out to be remarkably constructive.

wof collage Hearing about some of the best examples of low- to middle-income countries that have taken well-planned, system-wide, sensibly financed steps to get the widest possible access to the best possible early detection, treatment and follow-up showed just how much can be achieved for cancer patients, even with modest resources, by simply getting the fundamentals right.

While hearing about the cost, both in health expenditure and overtreatment, of squeezing out additional survival benefit for patients in better resourced health systems brought home how unsustainable current approaches to developing new treatments are becoming, even for world’s wealthiest countries. The message that came out was about priorities.

  • Don’t waste resources on expensive equipment and therapies if the money can be better used getting the fundamentals right for everybody who needs them.
  • Don’t waste resources on developing new therapies unless they aim high – which means tackling resistance rather simply chasing cancer cell evolution from dependence on one mutated pathway to the next.

Bold policy initiatives that champion the public interest will be needed at international and national level to achieve what must be achieved. The task of the 35 assembled experts, leaders and innovators in their own fields, was to spell out the core elements of such initiatives.

As keynote speaker Paul Workman, chief executive of the UK Institute of Cancer Research, points out in the video below, the level of agreement among participants was remarkable, given the differences in their geographic and professional backgrounds and the strong views held by all.

The exact wording of the final policy appeal is currently being finalised. It will be published on this blog and in the March issue of Cancer World, which will carry a full report of this remarkable meeting. It will also feed into a discussion at the ‘Davos’ World Economic Forum on meeting the challenge of the global cancer epidemic, if and when the organisers confirm that the issue has made it onto the final agenda at the end of January 2015.

Slides from most of the presentations are available now on the ESO website (access requires you to register with Club ESO).

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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An essential cancer medicines list for Europe

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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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