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ACCELERATING PROGRESS AGAINST CANCER ASCO’s Blueprint for Transforming Clinical and Translational Cancer Research NOVEMBER 2011 EXECUTIVE EDITORS Mark G. Kris, MD Neal J. Meropol, MD Eric P. Winer, MD ASCO PRESIDENT Michael P. Link, MD IMMEDIATE ASCO PAST PRESIDENT George W. Sledge, Jr., MD ASCO PRESIDENT-ELECT Sandra M. Swain, MD ASCO CHIEF EXECUTIVE OFFICER Allen S. Lichter, MD Table of Contents Imagining the Future: A Patient’s Experience..................................................2 INTRODUCTION A New Vision for Clinical and Translational Cancer Research.......................4 ASCO’S BLUEPRINT FOR ACTION......................................................................7 I. A New Approach to Therapeutic Development...................................................................7 II. Faster, Smarter Clinical Trials................................................................................................14 III. Harnessing Health Information through Technology.....................................................20 CONCLUSION The Way Forward................................................................................................ 25 GLOSSARY........................................................................................................... 26 REFERENCES.......................................................................................................28 Imagining the Future: A Patient’s Experience You visit your doctor for your annual physical. She asks you to undergo a routine blood test. You wait a few minutes for the test to process and are called back to hear the results. She tells you that the test detected cancerous cells in your bloodstream, which are an indication of an early-stage cancer that is developing somewhere in your body. The doctor reassures you that since the cancer was detected at a very early stage, there is a good chance that it can be managed or cured. She refers you to an oncologist and recommends additional tests to determine the molecular “fingerprint” of the cancerous cells. This takes just a few hours, and will provide vital information about the gene and protein abnormalities that may be driving the cancer. When you meet your oncologist, he tells you that you have an early-stage cancer arising in the kidneys. But the tumor’s location isn’t really what he considers most important. In this molecular era of cancer treatment, what matters most is your genomic profile and the unique combination of molecular features of your cancer. In your case, the cancer is caused by a specific set of abnormal genes, which are disabling three key “hubs” in the vast network of molecular pathways that regulate the growth of your cancerous cells. As a result, the cells have become stuck in an “always grow” mode. Your oncologist explains the standard treatment options available to target these hubs. He also notes that your electronic health record (EHR) indicates that based on your medical history and genomic predisposition — and on information from other patients like you who have undergone these treatments — you will probably have an adverse reaction to one of the standard therapies. The EHR also identifies a clinical trial of a new therapy, for which you qualify based on your molecular profile. Your oncologist explains the risks and benefits of participating in the clinical trial, and you go home to think it over 2 Accelerating Progress Against Cancer and talk with your family. You review your EHR lab report and other personalized information on your computer and contact your local comprehensive cancer center’s second opinion service to review your options. With the second opinion confirming your doctor’s assessment, and feeling confident in your own knowledge, you return to your oncologist’s office, enroll in the trial, and immediately receive electronic confirmation with information on next steps. The treatment being studied in the trial includes two new drugs, which are attached to a microscopic “nanoparticle shuttle” that will deliver them directly to individual cancer cells, sparing healthy cells and minimizing side effects. You also receive a saliva reader that plugs into your smart phone, together with a few mobile applications that allow you to record your symptoms during the trial and send information automatically to your EHR. Every eight hours, your phone will buzz to remind you to take your medicine and answer a short series of questions about how you’re feeling. It alerts you that you should expect to be slightly fatigued and includes suggestions for managing this side effect. The next day, a nurse calls you to make sure everything is working properly and to answer any questions. He tells you he will be monitoring your progress throughout the trial, and will contact you if the answers you provide indicate anything out of the ordinary. He also reminds you that all of your doctors — including your primary care physician and cardiologist — will be able to track your status through your EHR, so they can continue to make fully informed decisions about your other health care needs. You feel reassured because your doctor and nurse know a great deal about the drivers of your cancer, and are helping you make informed decisions to manage your cancer while continuing to work and live an active life. ASCO’s Blueprint for Transforming Clinical and Translational Research 3 INTRODUCTION A New Vision for Clinical and Translational Cancer Research “We can no longer think of cancer as one disease. Even something like lung cancer could be hundreds of distinct cancers, each defined by specific molecular characteristics requiring different treatment approaches. This makes research more challenging, but the payoff for patients will be enormous.” Michael P. Link, MD, President of ASCO It has been 40 years since President Nixon signed the National Cancer Act into law.1 With this landmark legislation, the United States entered an era of rapid advancement in our understanding of cancer and our ability to prevent, detect and treat it. As a result, more people are surviving cancer than ever before, and quality of life for those with the disease has dramatically improved. 2 While advances have been extraordinary in many ways, there is an urgent need to accelerate the pace of progress. Many cancers are not detected until their latest stages, and others have resisted most attempts at treatment. As a result, cancer still kills more than 500,000 people in the United States each year3 and the disease is projected to become the nation’s leading killer over the next decade as the population ages. 4 Worldwide, the cancer problem is growing quickly. 5 With recent breakthroughs in technology and in cancer “panomics” — the combination of genes, proteins, molecular pathways and unique patient characteristics that together drive the disease — there is new hope and unprecedented opportunity to make more rapid advances. Yet our nation’s translational and clinical research system is unprepared to deliver on this promise. This report from the American Society of Clinical Oncology lays out a vision for an approach to clinical and translational cancer research that takes full advantage of today’s scientific and technological opportunities. If bold action is taken to achieve this vision, we can realize major new advances in cancer prevention, detection and treatment and improve the care of patients. The report makes the following case for action: yy Investments in cancer research have already saved and improved countless lives. While cancer has proved far more difficult to defeat than imagined when the National Cancer Act was enacted, today, two out of three people live at least five years after a cancer diagnosis, up from roughly one out of two in the 1970s. The nation’s cancer death rate has dropped 18 percent since the early 1990s, reversing decades of increases. 3 And people with the disease are increasingly able to live active, fulfilling lives, due to better management of symptoms and treatments with fewer side effects. yy Cancer science is in a period of revolutionary change. As a result of our rapidly growing understanding of the biology of cancer, treatments are increasingly targeted to the molecular “triggers” that cause normal cells to become cancerous. Researchers are using new technologies — from the fields of computational chemistry, imaging technology, nanotechnology, health information 4 Accelerating Progress Against Cancer technology and genetic engineering — to engineer therapies that target the multiple pathways that combine to drive a patient’s cancer, with hundreds of potential new targets yet to explore. yy Clinical cancer research and patient care could be vastly more targeted, more efficient and more effective. With recent advances, it is not unrealistic to imagine that over the next decade, clinicians will increasingly be able to choose therapies that target the characteristics of each cancer and each patient. In addition, cancer diagnosis will be earlier, and diagnostic tests will provide molecular information that informs treatment decisions and management of side effects. A growing number of effective treatments will be targeted to defined patient populations. And new drugs will be developed simultaneously with the diagnostic tools that are needed to guide their use. Treatments will be targeted not only at cancerous cells but also at pre-cancerous cells and the cell’s surrounding environment. Clinical trials will be launched and completed far more quickly. Every patient will have the opportunity to contribute to translational and clinical research thanks to advances in health information technology (HIT) that enable real-time collection and sharing of clinical information through electronic health records (EHRs). yy But this vision is possible only if we transform the way translational and clinical cancer research is conducted. The nation’s cancer drug development and clinical research infrastructures have not kept pace with recent advances. The clinical trials system has been weakened by a labyrinth of regulatory requirements and years of under-funding. Traditional trial designs and drug development models are insufficient to fully capitalize on the potential of molecularly-targeted therapies. And companies are discouraged from sharing ideas or testing promising new treatments in combination due to a lack of incentives and the absence of a clear process for collaboration.6, 7 Explore 40 Years of Progress in Cancer Research: ASCO’s CancerProgress.Net In May 2011, ASCO launched CancerProgress.Net, a dynamic website that provides an interactive journey through four decades of advances in the prevention, diagnosis and treatment of cancer. Created to mark the 40th anniversary of the National Cancer Act, CancerProgress.Net was developed under the guidance of 17 of the nation’s leading oncologists. Key features of the site include: • An interactive timeline of cancer research advances — covering 14 different cancer types and every type of care, from prevention to molecularly targeted therapies • “Data visualization” tools to help bring select cancer • Downloadable slides and links to other resources statistics to life • Expert interviews and historical commentary from renowned leaders in oncology The site is updated regularly to feature major new advances in cancer research and patient care. ASCO’s Blueprint for Transforming Clinical and Translational Research 5 About this Report This report from ASCO — which represents more than 30,000 physicians and other professionals who treat people with cancer and conduct clinical research — provides a high-level blueprint for transforming the translational and clinical cancer research system in the United States. It addresses three main areas in which changes are urgently needed: 1. Establishing a new approach to therapeutic development, driven by our more thorough understanding of cancer biology 2. Designing smarter, faster clinical trials that are appropriate for the era of molecularly-targeted therapies 3. Harnessing information technology to seamlessly integrate clinical and translational research and patient care, ensuring that every patient’s experience can inform research and improve care In each area, we describe the vision that ASCO believes can become a reality within the next decade and provide an initial blueprint for action. We also outline the steps ASCO plans to take to achieve this vision, and we invite stakeholders in the cancer research community (e.g., policymakers, patient advocacy organizations, professional societies, public and private research sponsors and regulatory bodies) to join us. Over the next three years, ASCO will work with partners throughout the cancer research community to develop more detailed plans of action for each of the three areas covered in this report. 6 Accelerating Progress Against Cancer Asco’s Blueprint For Action I. A New Approach to Therapeutic Development The Situation Today developing and testing new therapies is ill-equipped to capitalize on that new knowledge: For decades, the development of new treatments yy While new technologies are allowing us to decode for people with cancer involved choosing drugs for the genomes of a growing number of cancers, tumors based largely on their location within the body. researchers have a limited understanding of which Today, thanks to genomic advances and a deeper un- molecular pathways within a person’s cancer are derstanding of cancer biology, this approach is being most important to target. replaced with development of approaches that target specific molecular characteristics of the cancer cell yy Researchers also have a limited understanding of — the molecular “on-off” switches that are critical to how the cancer cell’s environment — for example, driving cancer cells’ uncontrolled growth. the molecular characteristics of the surrounding tissue — influences the cancer’s development and This targeted approach has already improved treat- spread. ment for many cancers, especially those that are driven by a single powerful mutation. One of the best- yy We do not have proven, easily detectable and known examples is breast cancer that over-expresses measurable biomarkers (see box, p. 8) to identify the HER2 protein. Once one of the most difficult can- patients based on the molecular characteristics of cers to treat, this form of breast cancer is now highly their cancer, or to monitor the effectiveness of pre- treatable, thanks to the development of drugs that vention and therapeutic strategies in real time. specifically block the cancer-fueling effects of HER2. 8 yy With molecularly targeted treatment and prevention For the vast majority of cancers, however, it has be- strategies, more information about each patient’s come increasingly clear that targeting a single molec- cancer is needed to identify the patients who are ular defect is not enough. Most cancers are driven by most likely to benefit from a given treatment. To multiple mutations that provide pathways for cancer realize the greatest potential benefits, development development, many or all of which may need to be of treatments should be accompanied by develop- targeted for the cancer’s growth to be prevented or ment of diagnostic tests to identify appropriate controlled. In addition, cancers that are ostensibly of patients and monitor the outcomes of those treat- one type — for example, lung cancer — can be driven ments in real time. Today, however, treatments and by many different molecular defects and require very diagnostics are not typically developed and tested different treatments. In short, there is no single breast at the same time. An additional complication results cancer or lung cancer or colon cancer, but rather sev- because therapies and diagnostic tests are regu- eral or even dozens of molecularly distinct cancers of lated by different government bodies. each type that can arise. yy Currently there is no consensus among researchWhile our understanding of this molecular basis for ers or research funders about the most urgent and cancer is growing rapidly, our current approach to promising priorities for therapeutic and diagnostic ASCO’s Blueprint for Transforming Clinical and Translational Research 7 development. As a result, there is widespread duplica- Biomarkers and Their Functions tion of effort in some areas, including “me-too” trials of therapies. In addition, trial sponsors often focus Biomarkers are substances or biological features on areas that are unlikely to result in major advances arising in tissue, blood or other bodily fluids that over existing options, while critical gaps in cancer can be easily identified and used to diagnose or prevention and treatment are left unaddressed. monitor a disease and its response to treatment. In practice, biomarkers are detected through yy With multiple molecular triggers for each cancer, it various diagnostic tests — for example, blood or is likely that a combination, or “cocktail” approach saliva tests, or imaging tools such as CT scans or to treatment and prevention strategies will be magnetic resonance imaging (MRI). required. Yet legal, financial and regulatory hurdles currently make it challenging for companies to work Perhaps the best-known example of a biomarker together to test promising combinations. is cholesterol level in blood, which serves as a marker for heart disease. Because of the strong yy Combining different strategies for prevention and link to heart disease, monitoring cholesterol in treatment of cancer will require teams of research- blood is an effective way to determine the effects ers. Academic incentives, however, reward individual of anti-cholesterol medications on reducing the research efforts over team approaches. risk of heart attacks. In cancer, biomarkers will increasingly serve ASCO’s Vision for the Next Decade several important functions. More and more, they will determine if a person is at increased risk for Within the next decade, ASCO envisions increasing re- certain cancers; enable physicians to diagnose liance on molecularly-driven, collaborative approaches some cancers at an early stage; and guide to cancer diagnostic and therapeutic development. treatment decisions. Development of new treatment and prevention strategies will be governed primarily by the molecular In cancer research, biomarkers are increasingly characteristics of the cancer, rather than its location essential to identify new treatment targets; in the body. New, more collaborative research models quickly identify patients who are eligible for and trial designs will enable testing of multiple drugs specific trials; and monitor responses to therapy. at once, and provide more meaningful insight into what does and doesn’t work, and why. Physicians and Current examples of cancer biomarkers include: researchers will have a robust set of biomarkers to • CA125 for monitoring response to ovarian guide prevention, diagnosis and treatment decisions 9 cancer treatment • Tumor glucose metabolism, as measured by PET imaging, to provide a more accurate for many more types of cancer. And new technologies will open the door to entirely new approaches to cancer prevention, detection and treatment. prognosis10 • HER2 gene expression to determine the The key elements of ASCO’s vision are as follows: likelihood of benefitting from targeted breast cancer drugs such as trastuzumab (Herceptin) Defining Cancer Based on Characteristics, Not and lapatinib (Tykerb) 8 Solely by Location in the Body Cancer will no longer be identified primarily by the location in the body where it begins, but also by its 8 Accelerating Progress Against Cancer