PROGRESS REPORT: Implementation of ASCO’s Blueprint for Transforming Clinical and Translational Cancer Research

In November 2011, ASCO issued a prescription for transforming clinical cancer research in the United States and speeding the creation of effective new therapies for patients. In its report, Accelerating Progress Against Cancer: ASCO’s Blueprint for Transforming Clinical and Translational Cancer Research, ASCO laid out a vision for a cancer research system that fully capitalizes on scientific and technological advances to deliver more effective and personalized cancer therapies faster.

Since issuing the report, ASCO has worked with partners to drive the report’s recommendations forward. Many other major stakeholders, including the National Cancer Institute (NCI) and the US Food and Drug Administration (FDA) – have also launched initiatives that will contribute to achieving the vision of the Blueprint. Together, these steps represent significant new momentum toward a research system that realizes the potential of precision medicine.

Progress is occurring despite growing threats to cancer research funding. Accounting for recent cuts due to the federal sequester, the budget of the National Institutes of Health is at its lowest level since 2000 when adjusted for inflation – a drastic reduction in America’s historical commitment to biomedical research. Continued budget cutting in Congress could soon reduce the nation’s investment even further, risking our scientific leadership at the very moment of greatest potential for new advances. In response, ASCO has called on the nation’s leaders to sustain the search for cures and better treatments against a group of diseases that affects or touches nearly every American.

New Approaches to Therapeutic Development

The Blueprint described a vision in which development of new therapies is driven primarily by the molecular characteristics of each patient’s cancer rather than only its location in the body. Since 2011, this vision has moved closer to reality. Recently, for example, researchers reported the discovery that endometrial cancers share many of the same molecular characteristics as hard-to-treat breast and ovarian cancers,1 creating the potential for therapies that would benefit women with a range of seemingly different diseases.

ASCO also called for therapeutic development to be driven by clearer priorities, increased collaboration, and new approaches to development of diagnostics and biomarkers. Examples of progress include:

• ASCO developing recommendations on clinically meaningful outcomes for trials: ASCO is currently nearing completion of consensus recommendations to help ensure that new cancer therapies provide meaningful improvements in patient survival and quality of life. The recommendations will identify specific, clinically meaningful goals that should refocus clinical trials of new therapies for breast, colon, lung, and pancreatic cancers on outcomes that would have the most impact on patients in the clinic. Outcomes were proposed by ASCO-convened working groups of researchers and patient advocates and then shared with medical professionals, patients, advocates, and trial sponsors during a recent public comment period.

Once completed in the coming months, ASCO intends for the recommendations to improve the prioritization of therapeutic candidates based on their potential to meet these outcomes in clinical trials, and to help shape the design of trials themselves. The current draft of the recommendations is available on ASCO.org.

• FDA prioritizes breakthrough cancer therapies: Through legislation passed by Congress in July 2012, the FDA created a program to speed development of “breakthrough therapies” for life-threatening diseases, including cancer. To receive this designation, a drug must show potential to offer substantial improvement over available therapies in preclinical or phase 1 research. The FDA then provides intensive guidance on trial design and ongoing coordination with the manufacturer to create the most efficient path to review. To date, the agency has granted the breakthrough designation to 30 therapies, of which at least 9 are for cancers, including lung and breast cancers, melanoma, and certain hard-to-treat lymphomas and blood cancers.2 ASCO and the FDA held a seminar on the regulatory path of the breakthrough therapies on May 30, 2013.

Faster, Smarter Clinical Trials

The Blueprint promotes a more flexible, nimble, and efficient clinical cancer research system in which trial design and participation are driven primarily by the molecular characteristics of a patient’s cancer. Key progress in this area includes:

• Progress in revitalizing federally funded clinical cancer research:In April 2010, the Institute of Medicine (IOM) released a landmark report calling for actions to modernize and strengthen the NCI Clinical Trials Cooperative Group Program, which has contributed many of the most important advances against cancer in recent decades. ASCO supports full implementation of the IOM report and has worked with IOM, NCI, and others to achieve this goal. Progress in the last 2 years includes:
  • Strengthening of the Cooperative Group Program: NCI has issued funding opportunity announcements for the new National Clinical Trials Network, which results from the strategic consolidation of the Cooperative Group Program. Under this consolidation, 9 previous adult research groups have reorganized to form 4 groups with a shared goal of conducting state-of-the-art cancer trials. The Network will also include a pediatric component. This streamlined approach promises more uniformity, greater collaboration, and faster completion of important trials. The first round of research grants under the new structure will be issued in March 2014. ASCO worked with the IOM to host workshops in March 2011 and February 2013 to ensure accountability, transparency, and open discussion concerning these changes.
  • Reorganization of NCI’s community-based research programs: NCI has also announced that it will consolidate 3 different programs that support clinical research in community-based oncology practices, where most US cancer patients receive their care. As part of the change, NCI will promote trials that incorporate emerging science and novel trial designs. ASCO supports the overall approach, while expressing concern that growing limits on funding for clinical trials will reduce the capacity of participating practices to address new requirements that they conduct research on cancer care delivery in addition to their clinical research.
• ASCO is developing recommendations to avoid unnecessary exclusion of patients from trials: ASCO
  is in the midst of an effort to help modernize and streamline eligibility criteria for molecularly driven clinical trials. The primary objective is to ensure that patients are selected for trials primarily based on their molecular characteristics, while avoiding exclusion from trials based on criteria that are less meaningful in the context of precision medicine – for example, because of prior cancers or brain metastases. An ASCO working group is currently collecting data and surveying experts in the field and plans to complete draft recommendations this winter.
• ASCO and FDA partner to advance surrogate end points: ASCO, other specialty societies, and the FDA cosponsored a series of public meetings in 2012 and early 2013 to discuss the use of surrogate end points for efficacy in cancer clinical trials. Such end points – including various alternatives to overall or progression-free survival – are critical to new trial designs that can provide meaningful data on patient benefits in a shorter amount of time. The recent meetings addressed minimal residual disease end points for certain blood cancers and pathologic complete response (pCR) in breast cancer. In the breast cancer workshop, experts discussed draft FDA guidance to encourage use of pCR in trials of neoadjuvant therapy. ASCO is looking to the FDA to finalize this document for breast cancer and to promote similar approaches in other areas.
• Innovative lung cancer trial breaks new ground toward precision medicine: NCI, together with Friends of Cancer Research, has developed an innovative trial for advanced lung cancer in which all patients are analyzed for molecular mutations and then directed to different arms, testing different therapies, based on their mutations. This biomarker-driven trial embodies many of the recommendations made in ASCO’s Blueprint.
• FDA is working to streamline data collection for new uses of existing therapies: In 2012, the FDA released draft guidance that would eliminate the need for research sites to collect and companies to submit data on already known, low-grade safety risks associated with expanded uses of already approved drugs. ASCO is sharing its feedback with the FDA as the agency works to finalize the document, which would help accelerate approvals of additional indications for marketed drugs, a common feature of the oncology landscape.

Harnessing Health Information Technology

When the Blueprint was issued in 2011, the potential of health information technology (HIT) to inform cancer research and care was only beginning to be realized. While major work remains to be done, ASCO and others have made significant strides in this area:

• ASCO’s Quality Institute completes prototype of CancerLinQ: This groundbreaking HIT initiative will fulfill ASCO’s commitment to develop a “rapid learning system” to achieve higher-quality, higher- value cancer care with better outcomes for patients. The CancerLinQ prototype, completed in March 2013, includes de-identified data on more than 150,000 patients with breast cancer and clearly demonstrates the feasibility of building the system. Lessons from the prototype will guide the development of CancerLinQ over the next several years.

While the primary purpose of the system is quality improvement of cancer care, there are many secondary opportunities to advance learning. For clinical and translational researchers, CancerLinQ will unlock an unprecedented wealth of anonymous data on cancer patient characteristics, treatments, and outcomes. Instead of relying solely on the 3% of patients who participate in clinical trials, researchers will learn from every patient’s experience and draw hypotheses for clinical research from the vast “real world” of cancer care. ASCO is developing strong data governance policies and protocols to assure ethical stewardship of this resource.

• Efforts are under way to improve sharing, analysis of cancer care data: ASCO is leading an initiative to develop standards for cancer care data and overcome the widespread inconsistencies that currently limit secure sharing of information between providers, patients, and researchers. ASCO hosted a summit in late 2012 to identify potential solutions and aims to issue new standards on breast cancer information later this year.

ASCO Pledges to Continue Working to Advance All of the Blueprint’s Recommendations in Partnership With Others in the Cancer Research Community

Looking to the future, ASCO has outlined the following as priorities for the next 1 to 2 years:

• Address federal research funding threats: Recent progress toward a 21st-century clinical research system will fall short of its potential unless investments in cancer research are sustained. Since the federal sequester went into effect April 1, NCI has already been forced to slash its 2013 budget by nearly 6%, reducing the number of new research grants and straining existing research efforts. Congress and the Obama administration must work to restore the nation’s historical, lifesaving commitment to cancer research.
• Develop CancerLinQ and establish responsible pathways for research: ASCO’s Institute for Clinical Excellence plans to move ahead with a phased development of the quality improvement system. ASCO is consulting with many stakeholders, including those in the research and regulatory communities, to understand the potential for the resulting observational data sets to inform the discovery and use of new cancer therapies.
• Continue to establish consensus on new research end points: ASCO is currently discussing topics for future workshops that will bring the research community together to identify and agree on surrogate end points for clinical trials.
• Implement ASCO’s upcoming recommendations for clinically meaningful outcomes and eligibility criteria: ASCO will work with stakeholder organizations to promote the use of these consensus recommendations to shape the design and speed the completion of clinical trials.
• Regulation of cancer diagnostics: ASCO will continue to work with the FDA to modernize oversight of molecular diagnostics that are vitally important for clinical decision making in the era of precision oncology therapeutics.

References
1. Cancer Genome Atlas Research Network. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497:67-73.
2. Breakthrough therapies. Information is drawn in part from the following industry announcements (as of May 28, 2013): LDK378 for ALK+ non-small cell lung cancer; Novartis press release, March 15, 2013. Ibrutinib for relapsed or refractory mantle cell lymphoma, Waldenstrom’s macroglobulinemia, and chronic lymphocytic leukemia; Pharmacyclics press release, April 8, 2013. Palbociclib (PD-0332991) for breast cancer; Pfizer press release, April 10, 2013. Lambrolizumab for advanced melanoma; Merck press release, April 24, 2013. Daratumumab for double refractory multiple myeloma; Janssen Research & Development press release, May 1, 2013. Obinutuzumab (GA101) for chronic lymphocytic leukemia; Roche press release, May 16, 2013.
See also from the FDA: www.fda.gov/RegulatoryInformation/Legislation/Federal FoodDrugandCosmeticActFDCAct/SignificantAmendmentstotheFDCAct/FDA SIA/ucm341027.htm.