The overall goal of the program is to accelerate declines in cancer mortality based on current knowledge and existing technology.
—Ronald A. DePinho, MD
I anticipate that we are going to continue to have declines in cancer mortality … mostly as a result of more intensive efforts in tobacco prevention and cessation, making a strong commitment to early detection and prognostication, and facilitating the development of immune checkpoint and targeted therapies, with guidance from in-depth profiles of a patient’s tumor.
—Ronald A. DePinho, MD
In 2012, just 1 year after taking the reins as President of The University of Texas MD Anderson Cancer Center, Ronald A. DePinho, MD, announced his plans to launch the Moon Shots Program, the most ambitious endeavor undertaken by the cancer center to dramatically accelerate the pace of reducing cancer deaths within 10 years. Inspired by President John F. Kennedy’s clarion call in 1962 for America’s space program to accomplish the goal of reaching the moon before the end of the decade, Dr. DePinho reasoned it would take that same kind of organized and focused effort to reduce cancer deaths by more than its current pace of just 1% per year.
The program is initially targeting eight cancers—acute myeloid leukemia, myelodysplastic syndrome, chronic lymphocytic leukemia, melanoma, lung cancer, prostate cancer, triple-negative breast cancer, and ovarian cancer—in efforts overseen by six Moon Shots multidisciplinary teams of basic scientists, clinicians, pathologists, computational biologists, and epidemiologists. Supporting the Moon Shots teams are a variety of scientific and technical infrastructure platforms, including adaptive learning in genomic medicine, big data, cancer prevention and control, and the center for co-clinical trials. Fully implemented last year, the first 10 years of the Moon Shots Program is expected to cost an estimated $3 billion.
The ASCO Post talked with Dr. DePinho about the goals of the Moon Shots Program, improving cancer mortality rates through reliable early-detection screenings, and using IBM’s Watson rapid-learning system to improve patient outcomes.
Please talk about the goals of the Moon Shots Program.
The overall goal of the program is to accelerate declines in cancer mortality based on current knowledge and existing technology. A subtext of that goal is to develop an optimized framework for the conversion of knowledge into new policies, new drugs, and new diagnostics that make a difference for patients.
That often requires organizational attributes that are not always present in a robust way in the academic setting, such as having large multidisciplinary teams work together in a goal-oriented manner, and well-defined collaborations across departments within and between institutions, and sometimes between academic institutions and other organizations, including government and private foundations. It’s also important to have technology platforms with professional expertise for execution as well as adequate financial resources guided by clear achievable milestones and goals.
Our primary goal—the deliverable, in a sense—is to assemble these teams and platforms to plan and execute large impactful projects with the potential to accelerate declines in cancer mortality by more than the current 1% per year. Importantly, such projects would be based on knowledge in hand today and enabled by major technologic breakthroughs that have come online in the past few years. The concept is to develop an ecosystem that ensures the systematic translation of knowledge into endpoints that matter for patients.
For example, we’ve known for more than 10 years that early childhood sunburns and tanning bed usage during adolescence results in a significantly increased risk of melanoma in an individual’s 30s and 40s. In fact, just 11 tanning bed episodes before age 20 increases a person’s risk of melanoma by 85%. Yet there are inadequate state and federal laws prohibiting access to tanning bed usage to children under the age of 18. So while we have clear knowledge of the carcinogenic effects of ultraviolet rays on our youth, we have failed to convert such knowledge into effective legislation that would protect our children from the harmful effects of that carcinogen.
For the cancer prevention and control Moon Shots platform, we brought academic scholars in prevention and melanoma together with private foundations and experts in legislative affairs to educate legislators here in Texas about the harmful effects of tanning beds.
That coordinated effort across disciplines and organizations resulted in Texas becoming the fourth state in the country with a law prohibiting tanning bed access to children under age 18. With our platform, we’ve since reached out to seven other states in the past year, and some have passed similar legislation.
Choosing the Targets
How did you choose the eight cancers for initial targeting in the program?
We went through a think tank process over 6 months involving hundreds of MD Anderson Cancer Center investigators. They assembled into integrated disease teams, each focused on one of a dozen or so major cancers that collectively cause approximately 90% of cancer deaths. I asked faculty this question: Is there actionable information known today that if simply applied to practice would accelerate declines in cancer mortality?
Teams were empowered to assemble the needed diverse expertise, receive adequate resources, and utilize professional platforms. The projects were judged on the basis of impact and feasibility. The peer-review team of 24 leading scholars from academia and industry was led by Frank McCormick,
PhD, FRS, DSc (hon) [Director of the University of California, San Francisco Cancer Center], who was President of the American Association for Cancer Research at the time.
Approximately eight cancers were selected on the basis of actionable information that if simply applied, would accelerate declines in cancer mortality within the next 10 years. Across the cancers, our investigators came up with about 50 flagship projects, of which 13 are now underway.
Do you know which cancer types you will target next?
We have just announced a request for applications to build additional Moon Shot teams, and I anticipate applications from our investigators focused on glioblastoma, pancreas cancer, bladder cancer, colorectal cancer, and head and neck cancer. We are also interested in [human papillomavirus]–associated cancers.
These projects in development will be provided with adequate seed support to assemble teams and expand platform capabilities to take on several major projects that if applied, would result not just in incremental science, but would actually have a clinical impact on the population level.
Do you have benchmarks that you hope to achieve in the next 5 to 10 years?
Yes, we do. In the case of legislation, our ultimate goal is to educate federal policymakers in Washington to consider policy changes that curb and ultimately ban access to tanning beds for people aged 18 and younger.
On the therapeutic front, when our planning team began, we were on the cusp of durable responses in advanced melanoma due to advances in immunotherapy. We now know that ipilimumab (Yervoy), an anti-CTLA-4 blocking antibody, results in a 23% sustained elimination of disease 10 years out.
We reasoned that combinations of drugs would do even better. And, indeed, the combination of ipilimumab and nivolumab, an anti–PD-1 antibody, shows impressive responses for the majority of patients. Thanks to the work of many, particularly James P. Allison, PhD [Professor and Chair of The University of Texas MD Anderson Cancer Center Department of Immunology], there is a solid likelihood that we will reach our goal of reducing mortality from advanced melanoma by at least 50% in the next 5 to 10 years.
In the context of our melanoma moon shot, we are conducting novel clinical trials that combine agents and have developed an immune therapy platform to monitor immune cells as patients receive such therapy. This will help us understand responses to specific combinations and guide therapeutic options more quickly in our clinical trials.
Potential of New Agents
With the Moon Shots Program, will it be possible to actually cure more cancers or have greater success in turning more cancers into chronic diseases?
I wouldn’t have used the word “cure” in the same sentence with cancer pre-2010. But I think that everybody is feeling that with more targeted agents, especially the immune-modulating drugs, we are going to have a significant impact on creating durable responses if not cures for an increasing number of patients with advanced disease.
The question is, how can we fully harness the potential of those game-changing agents? We don’t yet understand why some patients respond to these immune checkpoint drugs and others don’t, and we don’t yet understand how to combine them in the most effective way possible to increase remissions and cure rates. So those are some of the questions we, and others in the field will be sorting out over the next few years.
I am most excited by the signal of activity in early-stage clinical trials for these immune checkpoint inhibitors for lung cancer, bladder cancer, head and neck cancer, and colon cancer. These early results in some cases are similar to the melanoma responses, albeit, in a more limited number of patients, suggesting that for an increasing number of cancers, more durable responses are on the horizon over the next decade. At these early stages, however, it would be prudent to use the term “durable complete responses,” because these agents have not been in use for long, and we don’t yet know if these patients’ cancers will recur in the years ahead.
These immune drugs and other targeted agents are generating a lot of optimism. For example, the prostate cancer Moon Shot team has launched two trials with curative intent for at least 30% of prostate cancer patients based on preliminary data from early-stage clinical trials. In the case of chronic lymphocytic leukemia, ibrutinib (Imbruvica), the Bruton’s tyrosine kinase inhibitor, is impressive and clearly represents a potential breakthrough therapy with sustained responses for a large fraction of patients.
Early Detection Efforts
Please talk about improving cancer mortality through more accurate screening methods.
Early detection of cancer is another major focus of the Moon Shots Program. In one flagship project, a large multidisciplinary team is working hard to achieve a practical strategy for the early detection of lung cancer. In lung cancer, we know that we can achieve a 20% reduction in cancer mortality by screening heavy smokers and catching the disease earlier. Dozens of our investigators have come together from different disciplines in an effort to develop an early detection strategy for lung cancer that would be effective and economically feasible.
Based on a recent national trial, spiral computed tomography (CT) screening of 50- to 64-year-olds with a 30 pack-year history of smoking resulted in reductions in mortality that, if scaled, would save about 10,000 lives per year. Unfortunately, spiral CT and current image analysis yields about a 96% false-positive rate, making it clear that another test, perhaps a blood test, would need to be joined with spiral CT to reduce the false-positive rate. We also need better risk models to know whom to screen in the first place.
Our team is working on developing both solutions, and we are joining forces with other institutions in the United States, Europe, and Asia to find answers.
You are using IBM’s Watson supercomputer in the Moon Shots Program and are initially testing it in the treatment of leukemia patients. Do you have results from the pilot program?
Watson is just one of the analytics we are using to help physicians make clinical decisions and improve patient care. We have worked to reorganize our approach to even address how patients come into and flow through the system, how the bioanalytes are isolated from that patient, how the information from that patient is ingested into a big data environment, and how it interfaces with other types of information, including data from other patients and research to help drive the practice of evidence-based medicine.
We used data from 10,000 patients with leukemia to teach Watson about that cancer, and now this established platform works well for leukemia. In the next phase, we will add other cancer types and pilot MD Anderson’s Oncology Expert Advisor (powered by Watson) for use at institutions in the United States and around the world. We hope to elevate the quality of oncology care by assisting physicians to make better evidence-based medical decisions for cancer patients, particularly for those patients who can’t come to our cancer center in Houston or to one of our partner institutions in the United States or internationally.
Are you optimistic that there will be substantial improvement in cancer mortality in the next 10 years?
One of the greatest challenges we are facing is an aging population, and that aging trend is escalating. By 2025, there are going to be 1.2 billion people worldwide over the age of 60, and by 2030, the cancer incidence in the United States is going to rise by approximately 45%. I think that we could make a significant dent in that incidence rate if we do our best to end tobacco smoking, reduce obesity rates, and encourage sun protection.
Beyond prevention, early cancer detection has the potential to be a game changer when it comes to mortality rates. I believe that with today’s technology, early detection is going to become a reality. But early detection has to be coupled with prognostication. It is thought that the majority of older individuals possess aspiring cancers, but if discovered, one would need prognostic determinants to decide which cancers might be aggressive and cause lethality vs cancers that would lay dormant for decades.
I believe that the technology is at hand to enable early detection of many of the major cancers through a simple blood test. Such tests could be developed within the next 10 years and would have a significant impact on cancer mortality, but to generate them, we need a concerted effort and adequate dedicated resources.
I anticipate that we are going to continue to have declines in cancer mortality—no one can say for sure by how much, but there is a clear potential for it to be more than the 1% per year we have been seeing, even in the face of increased incidence. And that will happen mostly as a result of more intensive efforts in tobacco prevention and cessation, making a strong commitment to early detection and prognostication, and facilitating the development of immune checkpoint and targeted therapies, with guidance from in-depth profiles of a patient’s tumor.
This is a new era in cancer medicine. ■
Disclosure: Dr. DePinho reported no potential conflicts of interest.