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Going to the ‘moon’ and back in the quest for better cancer care

Cancer is often discussed in militaristic terms. Patients ‘battle’ against the disease. In 1971, the then US President Richard Nixon unveiled a ‘War on Cancer’. When current US President Barack Obama surprisingly announced a new cancer strategy in his State of the Union address in January of this year, he used less aggressive, and more aspirational, language. He described the need for a cancer “Moonshot”. The word struck a hopeful note, one rooted in the optimism of the ’60s and the famous pledge by then US President John F Kennedy to send a man to a moon.

US Vice-President Joe Biden has been placed on “mission control” to lead the project, according to President Obama’s address. The metaphor of the battlefield was replaced by one of aeronautical adventure.

“For the loved ones we’ve all lost, for the families that we can still save, let’s make America the country that cures cancer once and for all,” the President declared.

The big question after the President delivered the speech was whether this aspiration has any chance of being realised. Some questioned whether the aim was just a calculated attempt to bolster the legacy of his Presidency.

Focus

Doctors, researchers and patient advocates within the cancer field have welcomed the commitment, which promised, at the very least, a renewed national focus on the disease. Cancer remains the second-leading cause of death in the US and is expected to kill nearly 600,000 Americans in 2016, which approximates to 1,600 people every day. However, significant progress has been achieved in recent decades. Over the past quarter century, US cancer mortality rates have decreased by 23 per cent. An editorial for The New England Journal of Medicine in May, by the US National Cancer Institute (NCI) Acting Director Dr Douglas R Lowy, and NCI Director Francis S Collins, answers why an initiative such as the cancer Moonshot is needed now.

“We believe the time is right for a renewed surge against cancer because, thanks to the coalescence of new scientific insights and technological innovations, prospects for success are greater than ever,” according to the editorial.

“One instrumental advance has been a dramatic shift in our fundamental understanding of cancer. Work using tools and technologies arising from the Human Genome Project and data from the Cancer Genome Atlas and other studies has clarified that cancer is a disease of the genome. It has become increasingly apparent that knowing what driver mutations are present in a particular tumour is often more important than knowing which organ system it arose from. Genomic technology has also shown that although each tumour is molecularly unique, certain pathways are repeatedly affected — findings that have informed the design and use of a new generation of drugs targeting those pathways.”

Another promising area of progress has been immunotherapy, with the authors noting checkpoint inhibitors and chimeric antigen receptor T-cell therapies have been shown to induce remissions or even cures in people with treatment-resistant forms of melanoma, leukaemia and lymphoma, as well as late-stage mesothelioma and ovarian, lung, kidney, and triple-negative breast cancers. They acknowledge, however, that many solid tumours fail to respond well to these approaches and initially positive responses are not always sustained.

“Clearly, it will be a monumental challenge to figure out how to apply and build on all the recent advances in our understanding of cancer biology and new therapeutic approaches, while also making progress in prevention, screening and early detection,” according to the authors.

“The new cancer research initiative aims to make a difference in all these areas by addressing two overarching priorities: increasing the resources devoted to fighting cancer, and breaking down silos to unite the cancer-fighting community.”

Providing adequate funding for the initiative will be key to its success. Shortly after the Moonshot was launched, the US government proposed it would provide $1 billion in funding towards cancer treatment and research.

A total of $195 million would be provided immediately for new cancer activities at the National Institutes of Health (NIH) in 2016. The US government said it would propose to continue this initiative in 2017, with $755 million in mandatory funds for new cancer-related research activities at both the NIH and the FDA.

The US Departments of Defence and Veterans Affairs are also increasing their investments in cancer research, including through funding centres of excellence focused on specific cancers, and conducting large longitudinal studies to help determine risk factors and enhance treatment.

Within the US Department of Health and Human Services (HHS), these investments are intended to support research in areas such as prevention and cancer vaccine development; early cancer detection; cancer immunotherapy therapy; genomic analysis of tumour and surrounding cells; and enhanced data sharing.

The FDA will develop a virtual oncology centre of excellence to leverage the combined skills of regulatory scientists and reviewers with expertise in drugs, biologics and devices. This centre will expedite the development of novel combination products and support an integrated approach in evaluating products for the prevention, screening, diagnosis and treatment of cancer; support the continued development of companion diagnostic tests and the use of combinations of drugs, biologics and devices to treat cancer; and develop and promote the use of treatment methods created through the science of precision medicine.

New technology to develop drug libraries and screens for inhibitors against a wide variety of targets will also be supported, which will be of particular benefit for paediatric populations.

Childhood cancers

The initiative will intensify efforts to collect and analyse tumour specimens from the rarest childhood cancers, enlisting participation from the paediatric oncology community.

Clinical data about the course of disease and response to therapy will also be included to enable the research community to develop new approaches to treat childhood cancers.

A Vice-President Exceptional Opportunities in Cancer Research Fund will also be established. The proposed new fund will be focused on high-risk, high-return research identified by the collaborative work and new ideas stimulated by the research community as part of this work.

The exact details surrounding what projects will be funded, and how much funding will be provided, have yet to be revealed. The White House Cancer Moonshot Task Force, chaired by Vice-President Biden, will focus on making the most of federal investments, targeted incentives, private sector efforts from industry and philanthropy, patient engagement initiatives, and other mechanisms to support cancer research and enable progress in treatment and care.

The Task Force will work with a number of US federal agencies that have responsibility for basic, translational and clinical research; therapy development; regulation of medical products; and medical care related to cancer. To assist with the development of its recommendations, the Task Force will consult with external experts from the scientific sectors, including the National Cancer Advisory Board (NCAB), and reach out to representatives from the cancer patient community, academia, business, non-profit organisations, state and local government agencies, and other interested persons.

A Blue Ribbon Panel of experts has been established as a working group of the NCAB that will assist the board in providing advice on the Moonshot initiative. The Panel will provide expert advice on the vision, proposed scientific goals and implementation of the Moonshot.

The Panel has established seven working groups, which are developing recommendations for opportunities on the following topics: expanding clinical trials; enhanced data sharing; cancer immunology and prevention; implementation sciences; paediatric cancer; precision prevention and early detection; and tumour evolution and progression.

ASCO 2016

Dr Deborah Mayer of the Blue Ribbon Panel made a presentation at ASCO 2016 during a media briefing on the Moonshot initiative. Dr Mayer said how the Panel, and the Moonshot initiative, was working to a very tight deadline. The Panel will report the working group’s recommendations to the NCAB in late summer. The NCAB will review the Panel’s recommendations and send its report to the NCI Director, who will, in turn, submit a final set of recommendations to the Cancer Moonshot Task Force by September 2016.

The Task Force will announce final recommendations for initiatives to be funded under the Moonshot in early 2017, and funding will be awarded in summer 2017. In her presentation, Dr Mayer spoke of how currently, it takes up to 17 years for evidence to be incorporated into practice. She said that in order to improve cancer outcomes, it is essential to identify and test methods for more effectively disseminating and implementing information about new approaches for cancer prevention, risk assessment, screening, prognosis, treatment and survivorship after the diagnosis of cancer is made.

Speaking to the Medical Independent (MI) Dr Mayer said that the cancer community at large has been energised by the Moonshot initiative.  “We were not sure when he first announced it what it was going to mean,” she said.

“But I think as it is taking shape and as we are getting input from so many people, I think it is a chance to take stock of where we are, what is working, what is not working and see how can we catapult that up to make better progress.”

Some critics of the Moonshot initiative state that there is nothing new about it and it is merely building upon work that is already occurring. While the initiative is welcome, the contention is that it is not the landmark President Obama had indicated. Dr Mayer rejected this point of view.

“The Moonshot is about looking at aspirational goals, but also it is about looking at the very pragmatic issues of what we can address now that can make a big difference over the next few years,” she said.

“Obviously, it is going to take five years to know whether we were successful or not, but I am hopeful that we have the right people around the table; we are looking at reducing the barriers that exist and some of the silos between federal agencies and public-private partnerships to make a difference, and I think we are looking at the whole cancer continuum from beginning to end and looking at where the biggest gaps are that are ready to be addressed. There are a lot of activities that are going on that are really forward-thinking but they have been in isolation. This is a way to bring them in under a big umbrella to help make sure that the directive is moving forward in the way we are hoping for.”

Dr Mayer said that as of yet, the precise amount of funding to be made available to the initiative had yet to be determined.

“They are working on it,” she said.

“There is a lot of bipartisan support but the budgets have to get signed off, so we don’t know the real numbers yet.”

Dr Mayer believes the work earmarked by the initiative will continue, no matter who wins this year’s US Presidential election.

“I think whoever gets elected will continue forth with the work because this has bipartisan support and cancer affects everybody,” she argued.

“This is not a political issue, this is a human interest issue that needs to get addressed, no matter what your politics are.”

During the media briefing, Dr Richard Schilsky, Chief Medical Officer with ASCO, spoke about ASCO’s commitment to advancing the Moonshot. Dr Schilsky said that the reduction in resources for cancer research has created a challenging environment for the discipline. He stated that the purchasing power of the NIH and the NCI have reduced by 18 per cent and 21 per cent respectively since 2003, based on inflation. Extra funding through the Moonshot is vitally important, according to Dr Schilsky, in order for researchers to be adequately supported.

Dr Schilsky also said that certain projects recently commenced by ASCO perfectly complemented the work being done by the Moonshot. He gave the example of TAPUR, which is ASCO’s first precision medicine trial.

TAPUR is designed to evaluate molecularly-targeted cancer drugs and collect data on clinical outcomes to learn about additional uses of these drugs outside of indications already approved by the FDA.

The project is currently underway at 37 clinical sites, with additional sites to be added in the coming months. Nearly 100 clinical sites around the US have expressed interest in participating in the study.

Also, there are 17 marketed therapies available and eight drug companies are involved.

Since opening in March 2016, 18 participants have enrolled and are receiving study treatment, and 31 more have provided consent and are in, or have completed, the screening process.

According to ASCO, the TAPUR study provides substantial flexibility and opportunity for both patients and clinical sites to participate, by: allowing physicians to choose the tumour specimen/blood sample and genomic profiling test; using broad general eligibility criteria, rather than the restrictive criteria applied in most trials; and streamlining data collection and reducing the overall amount of data collected, in comparison to most trials.

The study also aims to learn from real-world prescribing practices, educate oncologists on how to use genomically-targeted drugs, and catalogue oncologists’ choice of genomic profiling tests.

ASCO also will collaborate with the Netherlands Centre for Personalised Cancer Treatment, which is conducting the Drug Rediscovery Protocol (DRUP) trial, a protocol very similar to TAPUR, which allows data sharing.

Outgoing ASCO CEO Dr Alan Lichter then presented the details of another ASCO initiative, CancerLinQ, a project which connects and analyses “real-world” cancer data from almost any electronic health record source.

It was stressed throughout the meeting how only 3 per cent of cancer patients participate in clinical trials. CancerLinQ provides a way in which the data from more cancer patients can be analysed. According to data released at ASCO 2016, 58 practices have signed up to the initiative. So far 1,000 patients are involved and 750,000 patient records have been collected.

Cure?

One word that was noticeably absent during the briefing was ‘cure’.  The aim to cure cancer was floated by President Obama during his State of the Union address, but since then, it has been rarely reiterated. The language has instead focused on achieving more realisable goals.

Prof John Crown, Consultant Oncologist, St Vincent’s University Hospital, Dublin, who attended ASCO 2016, said in his opinion, cancer will not be cured anytime soon.

“If it wasn’t for the immune therapies, I would say we are nowhere near curing cancer,” Prof Crown told MI in Chicago during the ASCO Annual Meeting.

“The immune therapies are giving us a good, solid, large minority of patients with a variety of cancers that are getting durable remissions and who might be cured. That, in itself, even if it gets no better than that, is worthwhile. But a huge amount of real research is going on in the mechanics of the cancer cell: the biology, the signal transduction, the membrane receptor — all of this stuff. A lot of this, I must say, is going to result in better treatments, but not cures. The key thing for those of us who wanted to see a cure for cancer is the immune treatments, because the other stuff in many ways is pointing out how hard cancer is to cure.”

But Prof Crown said that he very much supports the concept of the Moonshot initiative.

“You are never going to hear me being anything other than very supportive of more spending on cancer research,” commented Prof Crown.

“It is one of the best things that society does and we should spend more money on it. The big question you always have to ask is, getting the balance right between big science and the smaller investigators who often come up with the best discoveries. You have to walk a fine line; when you develop great big structures to do research it can be great, but you have to make sure it does not quash the innovation and the inquisitiveness of good individual researchers. Some of the very best research that has resulted in the biggest results for patients fails to get federal funding in America and there is research by charities and philanthropies, which is done very well.”

Biden

The Moonshot initiative is a passion project for the US Vice-President, whose son, Beau Biden, died of brain cancer last year at the age of 46. Indeed, in his State of the Union Address,  President Obama said it was the Vice-President’s work in the area that inspired the project. According to Dr Mayer, Vice President Biden is well equipped to provide the leadership needed to make the Moonshot a success.

“He has been heavily involved, he is a quick learner, he really understands this and he is moving us along at quite a pace,” she said.

The Vice-President delivered a keynote address at ASCO 2016. During the address, he said that a change in mindset among clinicians and researchers is required in order to make progress in treating cancer.

“It requires a lot more openness,” he told delegates. “Open data, open collaboration, and above all, open minds.”

He referred to his discussions with the American Association of Cancer Research.

“There appeared to be a consensus… to reward team science and bringing together the expertise needed to answer big questions without being limited by jealousies between disciplines, laboratories and institutions that promote research that delivers results for patients.”

Like Dr Mayer, Vice-President Biden underlined how, unlike many other projects, the cancer Moonshot has achieved bipartisan support.

“Not only is there international consensus, but this is the last bipartisan thing left in American right now,” he said.

“When the President announced me to run this Moonshot, immediately half a dozen of the leading Republicans in the House and Senate, all good people, called and said ‘what do we need?’ If I had announced we were going to provide for peace in our time, I wouldn’t have gotten a single call. But all kidding aside, this is a moment we have got to seize.”

The Vice-President’s speech featured one of the first public unveilings of the Genomic Data Commons (GDC), a public database for clinical genomic data overseen and funded by the NCI. The GDC, which is designed to facilitate the sharing of information about sequencing of tumours and response to treatment, will begin with genomic and clinical data for 12,000 patients. It will be managed and maintained by the University of Chicago, US.

The GDC will centralise, standardise and make accessible data from large-scale NCI programmes such as The Cancer Genome Atlas and its paediatric equivalent, Therapeutically Applicable Research to Generate Effective Treatments.

Galvanising force

The extent to which the Moonshot initiative will make a difference to cancer care is up for debate. Many of the projects announced during ASCO 2016 would have happened regardless of the Moonshot. However, the initiative has acted as a galvanising force for the cancer community.

It will also provide much-needed additional funding for research, which has seen resources diminish in recent years. The tight time scale will no doubt prove challenging, while the election of the new US President in November may disrupt the momentum the initiative has developed. But if it succeeds, despite all the odds, in achieving what President Obama announced in his State of the Union address, the project would surely be regarded as one of the greatest of all US Presidential legacies.

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