Although payer management of oncology has come a long way from the “hands off” policies of just 5 or 6 years ago, clinical pathway programs are still in their infancy. Nonetheless, these programs are evolving as a primary means by which payers intend to control drug utilization in cancer treatment.

Recent research conducted by HRA—Healthcare Research & Analytics, a market research consultancy based in Parsippany, NJ, reveals that clinical pathway programs have been initiated mostly by larger payers in the United States, with midsized and smaller organizations still working to define and implement pathways. Twenty-eight percent of the 47 unique managed care organizations (MCOs) participating in the research, covering more than 75 million commercial lives collectively, claim to have initiated a clinical pathways program, with the majority of the remaining plans (51%) highly engaged and interested in creating them (

		Figure 1. Payer Use of Clinical Treatment Pathways for Oncology

		Utilization of Clinical Treatment Pathways

	• Clinical pathways for oncology, while not yet widespread, are expected to take hold among a majority of participating MCOs in the immediate future — impacting over 100 million commercial lives.	

		MCO indicates managed care organization.

		Figure 2. Perceptions of Managed Care Payer Establishment/Promotion of Clinical Pathways for Oncologic Therapy

“We’ve seen increased member responsibility through a fourth tier with coinsurance. Going forward, I see potential for a 5-tiered structure with preferred agents in a limited number of areas,” stated a key opinion leader participating in HRA’s research, commenting on changes to oncology management. “The largest thing will be more incentives to oncologists for following pathways—bonuses for following pathways, global budgets for common tumor types. But, it’s unlikely plans will have proscriptive management based on creating step therapies or a preferred formulary; instead, they’ll give financial incentives for the oncologists to help control costs by following guideline-based care.”

Changing Paradigms in Managed Care— Oncology Management

, adopted a cross-stakeholder approach to assessing changes to oncology management, including payers as well as healthcare professionals. Surveyed medical oncologists expressed a lukewarm response to the presence of payer-initiated pathway programs. Sixty-one percent of oncologists were either neutral or only mildly positive regarding the practice of payer establishment/promotion of pathway programs (

). A notable minority were opposed to the practice.

“[Payers make it] very difficult to do any type of imaging studies needed to stage patients, and when you do treatments [payers] want patients to undergo basically a cookbook form of interventions, not focusing on individuals as much as they are algorithms,” stated one oncologist participating in the research. “So, they’re very algorithm- or protocol-driven as opposed to looking at the individual patient…you’re starting to take the decision- making away from the physician and giving it to someone that doesn’t know the patient.”

In fact, just 25% of the surveyed oncologists are working with payers on pathway programs, although an equal proportion of them are planning to do so in the near future (

Even among payer organizations that have established clinical pathway programs in oncology, the primary source of these programs has been the National Comprehensive Cancer Network guidelines, which the majority of surveyed oncologists claim to be following as a matter of practice. HRA’s research does not portend any major changes to this approach in the near term, although some oncologists have hinted at major plans approaching them for input toward the development of more customized guidelines.

		Figure 3. Oncologist Plans to Work With Payers on Clinical Pathways

	• One-fourth of surveyed oncologists are currently working with payers on their clinical pathways programs, and among the balance, just about half plan to. Collectively, this brings the possible future potential up to more than half of medical oncologists.

	• While large practices have been more frequently approached, oncologists from smaller and midsized practices are particularly interested in pursuing pathways programs with payers.

“In oncology…the guidelines, pathways, are not specific enough,” a key opinion leader participating in HRA’s research said. “All products are there, although some are second or third line.”

Payers engaged in clinical pathway programs primarily intend to financially reward oncologists for adherence to the pathways through pay-for-performance incentives (

). A minority expect simply to continue the practice of recommending that oncologists follow guidelines, without implementing any penalties or rewards for compliance; and a few organizations adopt the very punitive approach of preventing oncologists who do not adhere to the guidelines from network participation in their plans.

		Figure 4. Requirements of Clinical Pathways

		Percentage of Managed Care Payers Using or Planning to Use Clinical Treatment Pathways

	• The most common requirement concerning clinical pathways—especially in the future&mdash;is/will be to give physicians an incentive to follow the pathway, although a subset of payers expect that simple “encouragement“ (rather than incentives) will be the norm.	

	What Does the Future Hold for Clinical Pathway Programs?

Changes to oncology overall—highly expensive new treatments, targeted therapies, increased survivorship, and the decline of the “independent” practitioner&mdash;have created the perfect storm for greater payer control of a traditionally “hands-off” category.

Proponents of pathway programs tout their benefits in promoting appropriate use of medications—and in some cases, controlling costs. As one payer executive in the HRA study states, “…At the end of the day, [payers]…have to figure out what we can pay for. Our system is unsustainable and needs to base care on real, evidence-based choices. It will become very important to show our choices make sense, especially if we have many possible pathways.”

Opponents view pathways as limiting physician choices in patient care, inserting standardization of care when, in many cases, exceptions should apply.

“Some MCOs adopt [clinical pathways] because it’s ‘the right thing to do’ (the stated reason), and it helps keep a lid on costs (the unstated reason),” a payer executive participating in the HRA research said. “Guidelines are neat but not always correct, such as HRT [hormone replacement therapy]. I’m not sure if the practice will continue to grow, or where it will go if it does.”

Oncologists and oncology nurse navigators participating in HRA’s research both agree that payers have become far more active in their management of oncology over the past few years—a trend that is expected to continue. A majority of healthcare practitioners in the research remain vehemently opposed to payer involvement in prescribing decisions. Transferring prescribing “control” from the physicians to payers, an expectation of denials for coverage, and more sophistication and complexity in payer management tools all are cited as reasons to oppose payer involvement.

“When payment gets increasingly tight, the payers clamp down on care, and as Medicare denies more care, insurers will follow suit,” an oncologist participating in the research said.

Nonetheless, despite the opposition, some oncologists do see value in the exertion of greater payer control on oncology. Those who are more amenable to payer interventions claim that guideline-based care will lead to better, consistent care with less waste overall. The continued evolution of targeted therapy, and the prospect of payers funding testing for the appropriate biomarkers, also is noted on the positive side. And, there is some perception that guideline-directed care will help educate insurers on best practices in cancer care.

“More constructive control…” is how one oncologist describes increased payer management of the category. “Oncology is now becoming an expensive part of our healthcare system. Drugs are more and more expensive and patients are living longer; testing is more complex and expensive from the molecular level to the gross diagnostic testing level, such as x-rays.”

Another oncologist states that tighter payer controls “will establish [the] best pattern of care and dictate choice of [treatment].”

Regardless of opinion or position—across payers or providers&mdash;oncology is now a “managed” category. The question remains, however, will payers and providers be able to come together to design and implement appropriate management strategies that save costs while still providing the best in patient care? Only time will tell. 

Articles

Clinical pathway programs are evolving as a primary means by which payers intend to control drug utilization in cancer treatment.

Clinical Pathways: An Evolutionary Approach to Cancer Care

In response to the billions of dollars wasted each year in the United States on fragmented, ineffective, and uncoordinated care, some healthcare reform efforts have focused on integrating the delivery of healthcare.

 Today, millions of Americans receive their healthcare from integrated delivery networks (IDNs).

However, just what is an IDN? Today, there really is no single answer.

 “The phrase covers a spectrum of scenarios; it has not been defined and is actually used as a catchall phrase to cover a variety of types of healthcare arrangements,” explained health economist Mark Hornbrook, PhD, researcher with the Cancer Research Network and senior investigator and chief scientist at the Kaiser Permanente Center for Health Research in Portland, Oregon. Integration might take place vertically, across different levels of care, or horizontally, such as occurs with hospital mergers.

In practice, an IDN might coordinate and standardize clinical care, disease management, financial management, and human resources across all of its providers and facilities. Some IDNs develop and employ patient care strategies with the end goals of cost-effective improvements in health outcomes, quality of care, and efficiency.

 Evidence demonstrates that patient care strategies are more likely to be used by IDNs than solo practitioners.

According to the 2012-2013 National Committee for Quality Assurance (NCQA) private health insurance plan rankings, half of the nation’s top 10 ranked plans (N = 474) are IDNs that provide insurance and employ the doctors who serve their clients.

 The rankings were published in the November 2012 issue of Consumer Reports, which states,“Unlike traditional, independent fee-for-service doctors and hospitals that make money by doing as many treatments and procedures as possible, whether needed or not, integrated plans prosper by keeping their customers healthy and avoiding wasteful care.”

		Figure 1. Total Medical and Pharmacy Costs (per Patient per Month) for Patients With or Without Cancer

		Source: Reprinted with permission from Kolodziej M, Hoverman R, Garey JS, et al. Benchmarks for value in cancer care: an analysis of a large commercial population. J Oncol Pract. 2011;7:301-306.

In the United States, substandard, heterogeneous, and excessive cancer care adversely affects a number of important short- and long-term outcomes including survival, quality of life, and cost.

 The complex and multidisciplinary nature of cancer care makes it prone to system failures, such as inadequate hand-offs, poor communication, and lack of accountability between providers. 

 Additionally, the cost of cancer treatments— especially medical oncology and specialty pharmacy drugs&mdash;is notoriously high. Hence, strategies to promote their cost-effective use have become key elements of cost-reduction efforts (

In the 2012 market intelligence report, Academic Cancer Centers: Trends Impacting Key Account Management, Inside Oncology, LLC, predicted that by 2016, the majority of patients with cancer will be treated at IDNs and cancer institutions (

 Factors contributing to this trend include Medicare reimbursement rate reductions for community practices, loosened 340B drug pricing qualification criteria, and pressure to meet new quality and performance requirements of the Centers for Medicare & Medicaid Services (CMS).

 “CMS has put in quality programs that are really stimulating and motivating people to become more aware of quality of care and integrating care,” stated David Guy, managing partner at Inside Oncology.

Well-established cancer centers have been delivering integrated cancer care for years. Most of them offer patient care teams comprising a range of specialists, as well as a breadth of services at a single location. In this setting, however, care is generally limited to the cancer episode, not prediagnosis or posttreatment. Primary care of survivors commonly reverts back to a primary care physician who is not affiliated with the cancer care center. However, many cancer centers have begun to take a more proactive role in survivor care as its importance has gained recognition.

		Figure 2. Site of Cancer Care, Actual and Projected, 2006-2015

Site-of-care data from 2006 to 2010 sourced from the 2011 Drug Trend Report: The Express Scripts Research & New Solutions Lab. Projected site-of-care data from 2011 to 2015 generated by Inside Oncology, LLC.

		IDN indicates integrated delivery network.

		Source: Reprinted with permission from Inside Oncology. Academic Cancer Centers: Trends Impacting Key Account Management; 2012. http://www.insideonc.com. Accessed October 10, 2012.

Perhaps the truest form of integrated cancer care is the type delivered by the large full-service IDNs at the top of the NCQA rankings. These institutions offer care that extends beyond cancer diagnosis and treatment to targeted detection, prevention, and survivorship care.

 This version of integrated care is in accordance with the Commission on Cancer’s (COC) Cancer Program Standards 2012: Ensuring Patient-Centered Care, which mandates care throughout the cancer continuum, from prevention through end-of-life care or survivorship.

 Cancer centers may provide prevention and screening services, but often these services are offered at the community level and not targeted to specific patients. These stand-alone interventions, while beneficial, may not be as effective overall as those delivered as part of an organized program integrated into comprehensive long-term patient encounters.

In other models of integrated care delivery, community oncologists are banding together into statewide or regional conglomerates such as Regional Cancer Care Associates (RCCA) of New Jersey, formed in January 2012. According to RCCA president Andrew L. Pecora, MD, by the end of 2012, the group will provide care for about half of patients newly diagnosed with cancer in the state of New Jersey. Among the initiatives being implemented by the group are cost-conscious protocols, networkwide integration of electronic medical record (EMR) systems, real-time overall and progression-free survival tracking software, and survivorship care planning in collaboration with local primary care physicians. “If I was to do this as a single doctor in my individual practice, it might be interesting; if we are doing it in an entire state…we will move the needle,” said Pecora.

In another model aimed at community oncology, McKesson Specialty Health offers tools to support delivery of integrated cancer care by practices belonging to The US Oncology Network, which is one of the nation’s largest networks of community-based oncology physicians. “For more than 15 years our affiliated practices have been pulling together resources our patients need into a single building in the community setting,” said Matt Brow, vice president of public policy and reimbursement strategy for McKesson Specialty Health. Brow said it is important to distinguish this type of quality- and value-driven initiative by oncologists from the trend of hospital systems buying up everything in their vicinity. For radiation oncologist Gregory Patton, MD, practice president, Compass Oncology in Portland, Oregon, being part of The US Oncology Network has been beneficial in terms of the resources and skilled professionals it offers. “The strength of the network is that its leadership and initiatives evolve from the practices,” he commented.

J. Russell Hoverman, MD, PhD, medical director of managed care for The US Oncology Network, discussed the challenges of delivering truly integrated care in the community setting. “We have a lot of things in our network that would fit into IDN but they are not all in the same place,” said Hoverman. Moving forward toward integration that is more complete will require cooperation with groups outside of their network, platforms for communication, incentives, and perhaps, payment change. “We are continuously looking at models in which we could do all this; I think we all agree this is the direction we need to head.” He also discussed how he would like to form long-term relationships with payers, rather than 1- or 2-year relationships, so they can collaboratively learn from and build on existing pathways and integrated care processes.

Well-designed, integrated cancer care systems are positioned to provide the types of services increasingly being recognized as essential to good cancer care by performance monitoring groups like the COC.

 Proponents of healthcare systems that integrate care throughout a cancer patient’s life journey talk about the benefits of team care, quick response, accountability, research integration, and systematic implementation of medical evidence, as well as the facilitation of screening and early detection programs.

 Ultimately, the benefits of integration should improve survival outcomes for patients. Cancer care delivery organizations are beginning to look beyond surrogate quality indicators to primary health outcomes. Kaiser Permanente’s most recently reported 5-year cancer survival rates were higher than the national average—in some cases 10% higher&mdash;for nearly every disease state (see 

 “It is not just that we have great oncologists, but also because we do a lot of screening, prevention, and proactive patient support,” said Joanne Schottinger, MD, assistant medical director for Quality at Kaiser Permanente in Southern California. “Our patients are with us an average of 17 years; these people do well not only because they saw us as a cancer patient, but also because of the care they received outside of that phase. Everything else that needs to be done is being supported. It is an integrated network that leads to results like that.”

		Figure 3. Overall 5-Year Melanoma Survival Rates of Patients With Melanoma Within the Kaiser Permanente Southern California Health Plan Compared With US Average (2002-2008)

		Survival can be calculated by different methods for different purposes. The survival statistics presented here are based on relative survival, which measures the survival of cancer patients compared with the general population to estimate the effect of cancer. The overall 5-year relative survival for 2002-2008 from 18 SEER geographic areas was 91.2%. The 5-year relative survival by race and sex was 88.9% for white men, 93.4% for white women, 62.5% for black men, and 78.5% for black women (

http://seer.cancer.gov/statfacts/html/melan.html#survival

). KP indicates Kaiser Permeuante; SEER, Surveillance, Epidemiology and End Results.

		Source: Reprinted with permission from Kaiser Permanente. Letter from the CEO, George Halvorson. Celebrating cancer care successes at Kaiser Permanente. July 6, 2012.

With a heavy focus on early detection, Kaiser Permanente has set an organizational goal of having the lowest number of stage 3 and 4 cancers in the country. Its fully integrated EMR system was customized to fit its oncology needs and features tools that make every single patient visit, for any purpose, an opportunity to deliver clinical prevention services or to schedule a screening. Through its organized colon cancer screening program, which includes mailed fecal screening kits, the number of colon cancers detected at the treatable stages of 0 or 1 has improved to 41%, which is a 28% increase. Likewise, the number of late-stage colon cancers detected has decreased by 32% to just 13%. This work extends to other cancers as well (eg, breast and cervical), in which similar results have been garnered. According to Schottinger, they also attribute positive outcomes to robust prevention programs that focus on smoking cessation, alcohol use reduction, and overall wellness.

Through their EMR systems, IDNs share standardized point-of-care decision support, protocols, and patient information among all healthcare personnel within a network. “Being within an organized IDN offers opportunity for better care for patients and better communication through EMRs. These systems are organized so that providers can manage cases together,” said Guy. New health information technologies will allow organizations such as RCCA to share patient electronic health information across multiple disparate EMR platforms, avoiding the need for groups who have already made an investment in an EMR system to make changes.

EMRs have contributed greatly to standardization of cancer care across large provider networks through incorporation of continuously updated evidence-based treatment pathways. The US Oncology Network, a pioneer in this area, has published studies documenting maintained outcomes with improved practice standardization and reduced costs through the use of cost-conscious pathways that are disseminated network-wide via their proprietary electronic health record system.

IDNs that use EMRs in conjunction with a team-based approach have also been able to enhance quality assurance and reduce chemotherapy-related error rates. Oncology pharmacists at Kaiser Permanente who monitor and manage patient safety have prevented 99.7% of patients with poor renal function from getting worse and 95.9% of patients on chemotherapy from developing anemia.

Furthermore, EMRs have advanced the power of clinical research programs within the IDNs. Hornbrook explained that the benefits have been tremendous in terms of increases in the availability, accessibility, and amount of data, as well as reduced workload (eg, chart abstractions). “We can do translational research out of (our EMRs),” said Schottinger. “That is really an exciting part for us…we get to look at how real people are responding to these regimens in the real world and build in the support that they need.” IDNs are capable of rapidly disseminating and deploying not only their own research-based safety responses, but also any externally issued medication or device safety alerts.

Nonetheless, not all efforts at integrated health delivery are going to be effective. As discussed in a recent report by the US Government Accountability Office, the delivery of high-quality care must be the mission at the outset.

 At this point, clear documentation associating cost and quality outcomes with IDN-provided care is not available.

 The variations in the extent of clinical and financial integration of existing IDNs make evaluation, comparison, and metaanalyses difficult. “The field is still in its infancy in terms of measuring what integrated care is, what it should be, and what expectations should be,” said Hoverman.

Growing evidence suggests that consolidation of healthcare providers and hospitals in a market opens the door for the resulting health system to charge payers more for their services and reduces market pressure to provide patients with value-based, high-quality care.

“When cancer doctors are employed by hospitals, costs go up in spades,” said Brow. He based this statement on reports prepared by healthcare consulting firms Avalere Health and Milliman that analyze site-of-service—related costs of cancer care.

 “The bigger a health system gets, the more leverage it has against the payer, the more indispensable it is to the payer,” said Brow.

Hospital systems argue that the higher reimbursement rates they receive for delivering chemotherapy are offset by other services they provide that are not available at private oncology practices, and by the fact that they are required to care for larger numbers of uninsured and underinsured patients. On the other hand, said Guy, the current fee-for-service model also incentivizes community oncologists to use the most expensive drugs to maximize reimbursement.

A 2010 report by AcademyHealth cited some of the potential clinical benefits and elimination of duplicate services that can result from integrating services for patients within a single organization.

 Nonetheless, some motivations for integration may be geared toward increasing volume and revenue, not cost containment or quality improvement.

 Evidence suggests that consolidation motivated by reasons other than efficiency will not garner efficiency.

			United States Government Accountability Office. Health care delivery: features of integrated systems support patient care strategies and access to care, but systems face challenges. GAO- 11-49. 

. Published 2010. Accessed October 10, 2012.

			Bach P. How many doctors does it take to treat a patient? 

			Kelley R. Where can $700 billion in waste be cut annually from the US healthcare system? 

			Enthoven AC. Integrated delivery systems: the cure for fragmentation. 

			National Commission for Quality Assurance. NCQA’s health insurance plan rankings 2012- 2013: private plan details. 

http://www.ncqa.org/Portals/0/Report%20Cards/Rankings/ hpr2012privatedet.pdf

. Published September 20, 2012. Accessed October 10, 2012.

			Health Insurance. Consumer Reports. November 2012:40-49.

			Hewitt ME, Simone JV; National Cancer Policy Board (US). Ensuring Quality Cancer Care. Washington, DC: National Academies Press; 1999. 

http://search.ebscohost.com/login. aspx?direct=true&scope=site&db=nlebk&db=nlabk&AN=14721

			Commission on Cancer. Cancer program standards 2012: ensuring patient-centered care v1.0. 

http://www.facs.org/cancer/coc/standards.html.

 Published 2012. Accessed October 10, 2012.

			Clauser SB, Wagner EH, Aiello Bowles EJ, Tuzzio L, Greene SM. Improving modern cancer care through information technology. 

			Bickell NA, LePar F, Wang JJ, Leventhal H. Lost opportunities: physicians’ reasons and disparities in breast cancer treatment. 

			Kolodziej M, Hoverman JR, Garey JS, et al. Benchmarks for value in cancer care: an analysis of a large commercial population. 

			Inside Oncology. Academic cancer centers:trends impacting key account management; 2012. 

			Association of Community Cancer Centers. Cancer care trends in community cancer centers: a survey of ACCC membership 2012. Published 2012.

			Hewitt ME, Greenfield S, Stovall E; National Cancer Policy Board (US). Committee on Cancer Survivorship: Improving Care and Quality of Life. From Cancer Patient to Cancer Survivor: Lost in Transition. Washington, DC: National Academies Press; 2006.

			National Commission for Quality Assurance. The state of health care quality 2011. 

http://www.ncqa.org/Portals/0/Publications/Resource%20Library/SOHC/SOHC%202011-v2- web_2.22.12.pdf.

 Published 2011. Accessed October 10, 2012.

			Levin TR, Jamieson L, Burley DA, Reyes J, Oehrli M, Caldwell C. Organized colorectal cancer screening in integrated health care systems. 

			Dalton WS, Sullivan DM, Yeatman TJ, Fenstermacher DA. The 2010 Health Care Reform Act: a potential opportunity to advance cancer research by taking cancer personally. 

			National Cancer Institute. Surveillance Epidemiology and End Results. 

			Neubauer MA, Hoverman JR, Kolodziej M, et al. Cost effectiveness of evidence-based treatment guidelines for the treatment of non-smallcell lung cancer in the community setting. 

			Hoverman JR, Cartwright TH, Patt DA, et al. Pathways, outcomes, and costs in colon cancer: retrospective evaluations in two distinct databases. 

			AcademyHealth. Research insights: integration, concentration, and competition in the provider marketplace. 

http://www.academyhealth.org/files/publications/AH_R_Integration%20 FINAL2.pdf.

 Published 2010. Accessed October 10, 2012.

			Alexander A, Garloch K, Neff J. Prices soar as hospitals dominate cancer market. Charlotte Observer, September 24, 2012. 

http://www.charlotteobserver.com/hospitals

			Jameson M. As hospitals take over doctors’ practices, fees rise. Orlando Sentinel, September 15, 2012. 

http://articles.orlandosentinel.com/2012-09-15/health/os-hospitals-buyphysicians-20120915_1_hospital-executives-hospitalemployeephysician-practices

			Avalere Health. Total cost of cancer care by site of service: physician office vs outpatient hospital. Avalere Health; 2012. 

http://www.avalerehealth.n/news/2012-04-03_COA/Cost_of_Care.pdf

. Published 2012. Accessed October 10, 2012.

			Finch K, Pyenson B. Milliman client report: site of service cost differences for Medicare patientsreceiving chemotherapy. 

http://www.communityoncology.org/UserFiles/pdfs/ millimansite-of-service-cost-differences-medicare-report.pdf

. Published 2011. Accessed October 10, 2012.

Is Our Healthcare System Ready to Integrate Cancer Care?

The American Association for Cancer Research (AACR) advocates that research is the best defense against cancer. In its 

 the AACR outlines important advances in cancer research, as well as the challenges the AACR is facing regarding funding. We had an interesting conversation with this year’s president, Frank McCormick, PhD, president and director of the University of California, San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center, and gained some insight into the coming year regarding what’s the next big area of interest in cancer research, and what the future holds for cancer research progress.

McCormick notes that one of the strategic priorities of the AACR is to expand its presence in the grass roots community, to increase awareness not only about the issues related to funding for cancer research, but also to include things people can do in terms of prevention, such as avoiding tobacco use and maintaining a healthy diet. Awareness, he advises, is to a greater extent legislative and involves policy issues, which most researchers can’t influence as effectively as they would like.

	Funding Concerns, Advocacy, and Research Advances

In addition to educational material for the public about cancer prevention, diagnosis, and treatment interspersed with stories from cancer survivors, the 

also includes discussions of some of the important recent advances in the development of targeted therapies, anti-hormone therapies, immunotherapies, patient stratification, and genomic medicine.

According to McCormick, one of the many challenges involved with cancer research is financial. The impact of the impending automatic spending cuts or “sequestration” proposed to occur in early 2013 would result in an approximate $400 million decrease in funding for the National Cancer Institute. First-time investigators just getting started would be severely hit hard by this slash in cuts, impeding significant future innovation.

Moreover, the impact of sequestration on the National Institutes of Health would reduce funding by approximately $2.52 billion, resulting in about 2300 fewer grants receiving awards in the fiscal year 2013. According to McCormick, “This would be a disaster and is something that is of major concern to the whole community, not just because of all the careers of people who will be affected, but also the fact that this is a moment in the history of cancer research when we are really getting a good bead on how complicated things are and how many opportunities there are to make progress.”

Sequestration would also severely affect the Centers for Disease Control and Prevention, the Food and Drug Administration, the Agency for Healthcare Research and Quality, and the National Science Foundation.

McCormick identified three of the hottest areas of interest in cancer research for 2013:

 The objection to personalized medicine is that physicians feel they have always practiced personalized medicine. 

 captures the precision of new technologies. “We are all talking about same thing,” says McCormick, “that is, identifying who is likely to benefit from specific drugs and who should be excluded, and tailoring drugs to individual patients.” A good example of this would be non-small cell lung cancer, which has had a very poor prognosis. Today, several subtypes of the disease have been identified that respond fairly well to targeted therapies. Therefore, physicians are obliged to run companion diagnostics to determine if patients have mutations in 

McCormick believes that sooner or later it will be faster and cheaper to sequence the whole genome and make decisions based on that rather than by using dozens of tests. He anticipates that every large medical center will one day be able to sequence every gene in every tumor, and notes that the FDA is aware that this is on the horizon. In the era of the $1000 genome, this would yield 105 times the information obtained from one gene mutation test, and at a much lower cost.

Patients who come to the clinics at UCSF are already seeking to have their tumor genome sequenced. McCormick acknowledges that the computer power to store and analyze this amount of data is an area of technology that’s struggling to keep up with all of the information. McCormick thinks it’s possible that polymorphisms in normal, healthy tissue may predict the response to targeted therapies, conventional chemotherapy, and radiation therapy. This means that a future complete workup would include completely sequencing normal tissue, tumor tissue, and, ideally, metastases. “It’s mind-bogglingly complicated and expensive, but that’s the future of predictive medicine,” he says.

In the next year or so, McCormick predicts, the big breakthrough discoveries that will affect patients directly by providing a survival benefit will be in immunotherapy. He expects to see results from secondgeneration approaches to affecting immune checkpoint genes or proteins that normally suppress the immune response in cancer patients, and looks forward to reports of benefits from relieving those checkpoints. He notes that in cancers with poor prognoses such as malignant melanoma, and possibly lung and renal cancer, some patients are surviving long enough that they might be considered cured. The challenge here is to figure out why 20% of patients respond and 80% don’t, and how survival can be increased by understanding the molecular basis of the responses and the nonresponses. That is a research field that wasn’t even possible until a few years ago because there weren’t enough responders to generate enough data to be analyzed. Now, the focus will be on biomarkers of responders and how they can be used to predict who is going to respond, and how the potency of antitumor agents can be increased so more patients have a long-term response. “It’s a fantastically fruitful area of research which wasn’t even thinkable a few years ago,” says McCormick.

For immunotherapy, it’s not clear whether differences in response are due to differences in the tumors themselves or in the host immune system or other aspects of the host makeup. Here, too, genes involved in the whole immune system and its regulation and expression, as well as genes actually in the tumor, will eventually be sequenced to try to determine who is likely to respond best.

Epigenetics is a field of study McCormick finds hard to deal with. He likes the concept that mutations lead to changes in proteins, which then may lead directly to the development of specific therapies. It is more difficult to figure out how changes or modifications to histones and chromatin structure translate into effects on tumor cells. As more and more sequencing is carried out on tumor genomes, more and more mutations in genes that affect these pathways are being identified, giving this area of research a more genetic underpinning. This is also resulting in a better sense of an epigenetic code and the impact this has on treatment. McCormick speculates that after the current first wave of cancer targets from the kinome, one of the next waves of drug targets might come from analysis of proteins involved in regulating the epigenome. Although drugs are being developed based on chromatin remodeling, genome plasticity, and methylation, the biology is complicated, and it will require a lot more validation and biological understanding, but it is definitely going happen.

McCormick expects therapies based on targets from the epigenome to be featured in the next year or two in the 

. Another aspect of cancer therapy that will play out over the next several years will be the results of combination treatments using targeted therapies. This will require a very sophisticated level of understanding to figure out how to make these pathways work together. “We can expect to see a whole range of discoveries there,” McCormick says, “I’ve been around a long time, and every few years some major innovation comes along which completely changes the way we think about how we do research and how we see therapies in ways which nobody previously anticipated, such as recombinant antibodies, cloning, PCR, siRNA, and so on.

“Those game-changing technologies keep on coming as long as the research world is well funded and supported. It may be difficult to predict the future, but I am confident that innovations will keep on coming, and that as long as that momentum is maintained, we will have a much more dramatic impact than what we can foresee by extrapolating from today,” concludes McCormick.

An interesting conversation with this year's AACR president, Frank McCormick, PhD, on the next big area of interest in cancer research, and what the future holds for cancer research progress.

April 2013 | Oncology Business News®

Clinical Pathways: An Evolutionary Approach to Cancer Care

Is Our Healthcare System Ready to Integrate Cancer Care?

AACR President Frank McCormick, PhD, Reflects on Past Progress and Looks to the Future

April 2013 | Oncology Business News®

Clinical Pathways: An Evolutionary Approach to Cancer Care

Is Our Healthcare System Ready to Integrate Cancer Care?

AACR President Frank McCormick, PhD, Reflects on Past Progress and Looks to the Future

Is Our Healthcare System Ready to Integrate Cancer Care?