Cancer – Breaking Through

Dr Haber – This is a hugely exciting time in the field of oncology, with treatments progressing from the laboratory to the clinic at unprecedented speed. We now know a large amount about the genetics of cancer. Treatments have changed radically – from the old world of ‘small molecules’ or chemically-based drugs, to biological treatments – an engineered cell, or an antibody. And the worlds of diagnostics and therapeutics are evolving together, which is hugely exciting and challenging.

In the field of biological treatments, one of the big advances has been in “immunotherapy” – using the patient’s own immune system to fight cancer. There are three basic types.

The first is essentially taking the brakes off the body’s immune system. This is effective if the body can recognise the cancer as foreign. The downside is that the immune system can also attack normal cells, causing potentially serious side effects. However, these treatments can be dramatically effective, so the pay-off can be worth it.

The second is if the cancer expresses a unique protein, immunotherapy can target every cell in the body expressing that protein. The patient’s immune cells are collected from the blood,  re-engineered to target the unique protein, then infused back into the patient’s blood to attack the cancer cells – a very complex and high-tech approach called CAR T-cell therapy.

The third is in very early development – cancer vaccines. The differences between cancer cells and normal cells can be very subtle. But if we can sequence tumour cells and predict what the immune system can recognise, it could potentially mount a response to something it hadn’t previously seen as foreign.

Mika Newton: For me, combining real world data (RWD) with real world experiences of patients is the future of care optimisation and the development of new tests and treatments.

Observing real world usage is the only way in which the value of combinations of tests and treatments can be realistically understood. The cost of a clinical trial to understand general utility in this way is just astronomical, so nobody will do it. The connection between diagnostics and the treatments they lead physicians and patients to pursue must be observed in the context of treatment. Integration of research and care then enables all parties to work quickly to make the most of the knowledge they are gaining.

When companies set up, or participate in, an appropriate mechanism for data collection and aggregation of RWD, they are able to understand what happens in the real world. Consequently, real world evidence offers the opportunity for a company to put their product into the marketplace and see emerging trends of both the perception/use/utility of technology and the context in which its value is maximised.

Real world evidence is rapidly emerging as the most efficient way to strategically understand the marketplace, communicate the value of products in the context of current care pathways, and to get regulatory approval for novel and incremental uses of products.

Many companies are using AI and Machine Learning to try to understand "big data." This may be useful in understanding what has been done in the past, but it doesn't give us data on the newest treatment options or on novel combination therapies. The "next level" for the use of AI isn't in analysing big data, but rather in telling us what data we need to advance knowledge, and to plan optimal experiments for acquiring that data with the fewest possible patients.

The use of AI in this way will power an "air traffic control system"—including garnering results from myriad investigator-initiated trials and investigator-sponsored trials—and from this, we can optimise the usage of the most valuable and limited resource we have for research: the patients.

Dr Martin – Many clients are also engaged in classical philanthropy in the oncology space. Compared to USD 133 billion in annual spend on cancer therapy, philanthropic dollars are much more limited however. The key questions for a donor are: where in oncology do you want to make a difference, and how can you direct your funding so it has leverage? To illustrate this, consider the GLOBOCAN database, which reported 18.1 million new cancer cases in 2018 and 9.6 million deaths from cancer. The estimates cover 185 countries. But for 50 countries, there is no historical cancer incidence data at all – data is estimated via statistical models. On the other hand, establishing a cancer registry does not cost more than 100’000-150’000 dollars per year per country. And a well-functioning registry is foundational to improving cancer control – this is an example of funding that creates leverage.

Another driver of progress is talent, and here philanthropy has a role to play as well. For example, our umbrella foundation for clients – Fondation Philanthropia – has funded doctoral research at the renowned Gustave Roussy Cancer Centre in France since 2013. There, a Ph.D. student “costs” 150’000 euros over three years. To date, all 22 laureates have found a research position, where they are already contributing to ground-breaking research in immuno-oncology and other fields.

Finally, moving beyond a “donation only” approach, our clients are also increasingly asking for investment tools to bring scientific advances to market faster. Here, a philanthropic intent paves the way to impact investing. To be more strategic with their investments, they ask “where can I create real change in the system? Drawing on the full toolbox, when should I make a grant, and when should I make an investment?” In this view, philanthropic capital is the ultimate risk capital and should be directed to do meaningful things the market wouldn’t do otherwise, including taking longer-term bets.

Thomas Casdagli – For me the most exciting breakthrough in recent years is the changed stance of the US Food and Drug Administration (FDA), which is responsible for new drug approvals. Around three years ago, the FDA radically changed the review process for drugs with a “breakthrough designation” – truly innovative treatments. These can now be developed, approved with smaller patient populations and delivered to patients much more quickly and cheaply. This is improving patient care, and introducing more competition in the market. Out of 43 new products approved in 2017, 33 were approved only in the US.

Dr Martin - I would say that breakthroughs in data are another key area of change - and how we are now gathering data from different countries. The hope is that as we gain a better understanding of this disease on a global level, that we can then ultimately make cancer research and treatment both more effective and more democratic, offering greater access to diagnostics and therapy across developed and developing markets alike.

Mika Newton – I would also choose the regulatory changes as the most exciting breakthrough too. Now we need to look at payment reform, and putting together the fields of data, technology, genomics and AI. This might be of particular help in bringing the best technology to market as we must be sensitive to the budget impact of any new technology.

Dr Haber – I think what is most remarkable these days is the unpredictability in the fields that have new breakthroughs and in the pace of change. It’s like you’re in a dark room and suddenly you find a flashlight. Treatment in some cancers has not changed that much in 50 years, but in others it has radically transformed. In five years, we might not recognise what we are doing today.

There have never been so many new cancer drugs approved, and more effective treatments available. On the other hand this rapid pace of discovery can lead to significant inequities and disparities in cancer care, both across academic and community hospitals within scientifically advanced countries, and from the developed to the developing world.

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