ASCO recently issued a report, Accelerating Progress Against Cancer: ASCO’s Blueprint for Transforming Clinical and Translational Cancer Research, which outlines the Society’s 10-year plan for improving cancer outcomes. Central to achieving that goal are three steps, including (1) therapy development based on the detailed molecular characterizations of each patient and his tumor; (2) designing smarter, faster clinical trials that provide evidence for effective treatments targeted to patients most likely to benefit; and (3) harnessing health information technology that integrates clinical research and all relevant patient information, such as tumor characteristics, site, and prior treatments. To succeed, the authors noted, collaboration is required from all stakeholders in the cancer research community, including public and private research sponsors, professional societies, the NCI and NCI-funded Clinical Trials Cooperative Groups, policymakers, patient advocacy organizations, and government regulatory agencies.
“The biggest challenge to success is getting the key constituencies to overcome inertia and to adopt and invest their energy in the possible. It’s very easy to continue on a path that we’ve been on for the past 20 years, and the challenge is for everyone to rethink together how we might do better on behalf of our patients,” said Neal J. Meropol, MD, Co-Executive Editor of ASCO’s Blueprint, and Division Chief, Hematology and Oncology, Department of Medicine, University Hospitals Case Medical Center, Seidman Cancer Center and Case Western Reserve University School of Medicine, Cleveland.
Over the next 3 years, ASCO plans to convene workshops with experts from all key groups to solidify plans for implementation of the Blueprint’s recommendations. ASCO’s Cancer Research Committee is organizing the first meeting to develop consensus on priorities for prevention and therapeutic strategies and biomarker development. ASCO is also working with the FDA on a series of meetings to discuss how minimal residual disease endpoints can be used to develop drugs for three types of leukemia—acute lymphoblastic leukemia, acute myeloid leukemia, and chronic lymphocytic leukemia—as a predictive surrogate for how patients will fare long-term.
“In chronic myeloid leukemia, for example, we can actually measure, with a fair degree of sensitivity in patients in remission, the depth of their remission. We know that minimal residual disease is a very, very highly predictive surrogate for how the patient is ultimately going to do. ASCO is helping to sponsor a meeting with the FDA to discuss how we can validate this information as a surrogate endpoint for the efficacy of new [leukemia] drugs,” said ASCO President Michael P. Link, MD, Lydia J. Lee Professor in Pediatric Oncology at Stanford University School of Medicine.
Smarter, Faster, More Effective Clinical Trials
Central to achieving extended patient survival rates and reducing cancer deaths is the design of targeted clinical trials based on the specific molecular characteristics of a patient’s cancer and the development of a multidrug-cocktail approach that targets the multiple molecular triggers for each cancer subtype.
“I think the whole clinical trial paradigm is going to change because we will have a combination of targeted agents that are almost custom-designed for each patient and we will see [quickly] whether the drug or drug combination is a success or failure. We hope to have a series of definitive trials in which we won’t have to wait 3 years to have an answer about a drug’s effectiveness. We should have the answer within months of accruing patients,” said Dr. Link.
Critical to the success of the new clinical trial paradigm is overcoming the challenges posed by the competitive and intellectual property concerns of pharmaceutical companies with regard to testing of drugs in combinations. In addition, the approval process for combination therapies will need to be worked out with the FDA. That said, there have been precedents for pharmaceutical companies collaborating in clinical trials of multiple drugs, including a phase I study of Merck’s AKT inhibitor MK-2206 and AstraZeneca’s mitogens-activated protein kinase 1 inhibitor AZD6244 in the treatment of solid tumors.
“Pharmaceutical companies are [increasingly] open to the idea of testing drugs in combination with a competitor’s product. The key element is that it has to ultimately make financial sense for their stockholders. One way ASCO can help is to work with the FDA to ensure that there is clarity regarding how joint development can occur in such a way that it is beneficial to multiple sponsors and at the same time minimizes their risk,” said Dr. Meropol.
Partnering with Patient Advocates
The ASCO report also calls on the FDA and pharmaceutical companies to recognize patients’ quality-of-life concerns in addition to treatment effectiveness as considerations for new drug approval and to include that information on drug labels. To develop a consensus on what constitutes “meaningful patient outcomes,” ASCO will work with patient advocates to bring together a group of experts from industry, biomedical research, NCI, FDA, and health insurers.
Looking ahead over the next decade, the report cites advances in health information technology as crucial to improving patient care and speeding research in molecularly targeted therapies. To accomplish those goals, ASCO is developing a rapid learning system for cancer care, which will house a secure central database of real-time patient-reported information, such as side effects from treatment, data from tumor biospecimens to allow physicians to assess the best treatment for each patient, and a system for alerting patients to appropriate clinical trials.
“We’re convinced that this Blueprint is the way forward to accelerating progress in cancer care and we will do everything possible to ensure its success,” said Dr. Link. ■
Disclosure: Drs. Meropol and Link reported no potential conflicts of interest.
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1. Kris MG, Meropol NJ, Winer EP (eds): Accelerating Progress Against Cancer: ASCO’s Blueprint for Transforming Clinical and Translational Cancer Research. Alexandria, Virginia; American Society of Clinical Oncology; 2011. Available at asco.org/blueprint. Accessed March 1, 2012.