This article appears in the September 2012 issue of HealthLeaders magazine.
When then President Richard Nixon in 1971 called for a "cure for cancer," he envisioned a crusade akin to the efforts that developed the atomic bomb and led to the moon landing.
But more than 40 years later, it has proven to be an elusive goal, and one that has changed dramatically over the decades. Now, the vision has transformed from seeking a singular cure for cancer to finding a multitude of cures for a complex disease that differentiates into the hundreds of types. The emerging singular focus now in the so-called war on cancer is personalized medicine, which involves tailoring drugs for each patient to attack that person's individual kind of cancer. Some have dubbed it one pill for one patient, or even named it individualized medicine. Others have a different take, describing it more as precision medicine, narrowing treatment for groups with certain ailments.
To pursue and exploit innovative technology, some health systems are developing service lines or special institutes for personalized medicine, with a focus on one-patient-at-a-time cancer care. While some healthcare systems are making slow and cautious moves into the frontier of personalized medicine, others are moving quickly in a this-is-the-future-right-now environment.
Some are moving ahead because they "perceive themselves on the frontier of the movement in personalized medicine," says Edward Abrahams, president of the Personalized Medicine Coalition, an education and advocacy organization based in Washington, D.C. "Not only do we hope systemic expenses can be cut with personalized medicine, but also the possibility of adverse events by targeting cost-effective diagnoses. Researchers will use tumor and patient genomes to find new therapies and drugs for individual patients."
There are economic gaps that personalized medicine advocates believe can be bridged over time, particularly related to government reimbursements. As of now, there are technological improvements for genomic sequencing that are reducing costs significantly, according to Maurie Markman, MD, senior vice president of clinical affairs and national director of medical oncology for the Cancer Treatment Centers of America, which has five acute care hospitals and is headquartered in Schaumburg, Ill.
"The future is here," Markman says, noting that there have been gradual and significant cost reductions for genome sequencing over the past decade or so. "Within the next year, it will be possible to sequence the entire genome of a tumor and the corresponding normal genome of an individual cancer patient for $3,000. Twelve to 15 years ago, it would cost about $6 million."
CTCA has contracted for genomic research with a biopharmaceutical firm, but does not have active clinical trials linked to the partnership yet. As part of its personalized medicine focus, CTCA includes available molecular-targeted therapy approaches for breast cancer and hormone screening, according to Markman.
Terry Hisey, vice chairman and U.S. life sciences leader for Deloitte, agrees that genome cost reductions are a "major tipping point" for development of personalized medicine and, like Markman, has seen reductions in time and money. "A few years ago, it took a year and $75,000 to do the gene sequencing of a person, and now it takes a day and $1,000," Hisey says. "In terms of care capability, it's going to help the industry with the number of therapies available. Things are happening to accelerate and enable it."
The approach to target drugs for care will reduce not only costs but the time it takes to get needed pharmaceuticals, says William Dalton, MD, PhD, founding director of the Personalized Medicine Institute at the H. Lee Moffitt Cancer Center in Tampa, Fla., and CEO of M2Gen. "Ultimately, this approach in personalized medicine will reduce costs by getting the drugs right the first time," he says. His organization, along with the Sanford-Burnham Medical Research Institute in Orlando, Fla., and the 2,224-bed Florida Hospital, also in Tampa, have a personalized program partnership for research and clinical programs.
"Too often, people are treated with the same regimen, and only a portion of the patients will respond," Dalton says. "It's almost a trial-and-error approach. The personalized medicine approach increases the probability that patients will respond the first time, and that's good for everybody."
While the genomic costs are decreasing, some note that the reimbursement system for diagnostic tests has not evolved to accommodate the advances.
"The cost of testing, the jury is still out on third-party payers," comments Matthew Ferber, PhD, assistant professor of laboratory medicine and pathology at the Mayo Clinic, a 1,150-bed organization based in Rochester, Minn. He also is codirector of the Clinomics Transitional Program within the clinic's Center for Individualized Medicine. Ferber is planning a personalized medicine service line with an initial focus on cancer patients where physicians have been stymied in their care.
"While there has been some real success, it's too early for insurance companies to say this is the standard of care. There is still more work to do. Insurance isn't going to cover to perform the lab tests. But the technology is causing a paradigm shift. There may be no ROI right now; it's the ‘I' for investment. You are looking at the future where we need to be."
Smaller organizations may face the "financial burden" of building an infrastructure for personalized medicine, and "they might want to let it mature," Ferber adds. By engaging in partnerships with pharmaceutical companies, however, hospitals and health institutions may ease that fiscal burden.
Moffitt Cancer Center's Dalton acknowledges the journey toward personalized medicine is a complicated one.
"Our biggest challenge is not the technology," Dalton says. "The technology is there. We can sequence the entire genome, at a reduced cost. That's not the challenge. It's what you do with all this information; how do you learn from it?"
Success key No. 1: A team approach
At the 537-staffed-bed Oregon Health and Science University Hospital in Portland, the Knight Cancer Institute has begun treating patients using personalized medicine specializing in cancer care, with a multidisciplinary team of physicians and researchers, according to Alan Sandler, MD, oncologist and professor of medicine in the division of hematology and medical oncology at the institute.
OHSUH saw success from the advent of personalized medicine in its backyard years ago.
A hospital physician, Brian Druker, MD, was among the first to develop personalized medicine drugs at a time the hospital was already collecting tumor information. The drug, Gleevec, was approved by the FDA in 2001, and is used to treat chronic myelogenous leukemia, a blood cancer that strikes about 5,000 people a year, and other cancers. The discovery of the drug was based on a specific genetic signature. Its usage has been linked to long-term survival of patients compared to alternative therapy, and is considered more cost effective.
The discovery "changed the course of the disease, adding years to the patient's life. It is also a pill, as opposed to intravenous chemotherapy," says Sandler.
The Knight Cancer Institute includes a multidisciplinary team of physicians who review treatment options with patients, with one added element: Researchers are involved with personalized medicine. The physician teams work closely with the hospital's diagnostic lab staff to analyze a patient's tumor for potential genetic abnormalities that may help lead to appropriate treatment. The advanced diagnostic testing allows researchers to examine genetic differences in the cancer cells.
As an example of the personalized medicine approach, the cancer facility highlights the case of a woman who previously had lung cancer but was later diagnosed with a brain tumor as well. KCI researchers found that the same changes in the cells of the lung were involved in spurring the brain tumor. Subsequent testing identified the exact mutations unique to the tumor, within the cell, and indicated a genetic defect. Using that information, KCI began to use a personalized approach for her care, and tailored drugs for her specific needs.
For a series of patients, a wide range of genes is analyzed, with hopes of generating genetic profiles. Like many facilities, OHSUH has not released the number of patients involved in its personalized medicine program, nor has it defined outcomes yet. That will be resolved when clinical trials are completed, Sandler says. There are a "number of different approaches using molecular targeted therapy," he says. For each patient, within a few weeks after diagnosis, the hospital obtains pharmaceutical information about drugs that may be suitable. "We start with more traditional therapy and that way we haven't lost any ground while waiting for information," Sandler says. The hospital also has biorepositories that store cancer tumor samples for future treatment decisions.
"A number of patients don't have mutations discovered yet," Sandler adds. "For those that do, we have some medication for them. At this point, some 'abnormalities' lack effective therapy. That's where we have the emphasis on clinical trials."
One of the most significant clinical trials involving the institute is known as the I-SPY 2 trial, which is testing the possibility of new therapeutic agents for cancer compared to standard chemotherapy. The focus is on women patients with newly diagnosed, advanced breast cancer. As part of the process, researchers are using genetic or biological markers from individual patient tumors that will be screened for potentially promising treatments.
"We have scratched the surface,'' Sandler says. "The concept of personalized medicine takes on a number of different approaches, and one that is most topical now is using molecular targeted therapy," he says.
Success key No. 2: Cooperative ventures
The Moffitt Cancer Center's Total Cancer Care program measures the expression of approximately 30,000 genes that make up a tumor to find the unique genetic fingerprint for each person. It has teamed up with the Sanford-Burnham Medical Research Institute and Florida Hospital to initiate medical research and clinical care in personalized medicine. In addition, it is forming relationships with as many as 15 community hospitals in 10 states in a consortium also designed to advance personalized medicine.
In February, Moffitt, Florida Hospital, and Sanford-Burnham announced collaboration on the Personalized Medicine Partnership of Florida. The partners were brought together to deliver what they described as the "complementary strengths" of the various organizations: Florida Hospital's large population, Sanford-Burnham's fundamental research expertise and technology platforms, and Moffitt's biospecimen bank, data warehouse, and personalized medicine capabilities, says Dalton, Moffitt's director.
While creating the Personalized Medicine Institute, Moffitt also developed a research arm, a for-profit biotechnology subsidiary called M2Gen, which serves as a repository where research tissues can be stored for long-term use. For an array of clinical trials in personalized medicine, Moffitt has enrolled at least 90,000 people in the program. It also has built an informatics platform "that allows us to categorize the tumors' genetic and genomic profiles," Dalton adds, referring to the collection of data focusing on patients' genetic makeup. "None of that existed when we started this. The capacity didn't exist."
To date, the center has collected 32,500 tumors and profiled 16,000 of those tumors.
While storing data to be analyzed by researchers for potential long-term cancer care, Moffitt also has begun to focus on cancer patients who relapsed, Dalton says. "We are working to define the best therapy for these, including clinical trials for these patients," he says.
Of the patients who have been invited into Moffitt's Total Cancer Care program, most accepted the offer to be included in personalized medicine, according to Dalton.
In developing the cancer care protocol, Moffitt formed a patient advocacy and ethics council to assist, especially for any questions related to personalized medicine. As part of that, Moffitt developed a patient portal to the data warehouse that provides patients with their own medical histories, data, and other significant information, Dalton says. Eventually, the portal also will be used to enable patients to make informed decisions.
"What makes the Total Cancer Care study more than just a repository and tissue bank," Moffitt stated in its annual report, which touched on its personalized medicine program, "is the effort to integrate the collection, profiling, analysis, and long-term storage of biological samples with other patient information, all gathered on a large ongoing scale with active follow-up for the rest of the patient's life." The report also noted that the National Cancer Institute awarded Moffitt a Specialized Programs of Research Excellence Grant for lung cancers. The report states that it "involves basing the selection of treatment and molecular and genetic characteristics of tumors using gene therapy."
By working with other hospitals, Moffitt is developing a "hub and spoke" model for improved personalized medicine care throughout the region, says Dalton. The hospital has a five-year plan "involving many other sites and partners. Our hope is to partner with other National Cancer Institute–designated cancer centers," he says.
Success key No.3: Focus on the intractable
The Mayo Clinic is initiating a personalized medicine service line with a focus on cancer patients where physician care has been stymied.
At least two Mayo Clinic facilities, in Florida and in Arizona, are engaged in clinical trials for patients with intractable cancer, such as those of the brain, kidney, liver, pancreas, and skin, and other cases with patients who have cancer with suspected underlying genetic conditions, according to Matthew P. Goetz, MD, associate professor of oncology and pharmacology at the Mayo Clinic College of Medicine.
The protocols will be included in the Mayo Clinic's Individualized Medicine Clinic, scheduled to open this fall at the three locations. Patients have been enrolled at Mayo Clinic Florida and Mayo Clinic Arizona for a pilot on whole genome sequencing, although final numbers have not
been released.
While the clinical trials are under way, patient care will be evaluated, Goetz says. The plans include multidisciplinary approaches, including a team of oncologists, as well as genomics and cancer researchers. The Mayo Clinic's centers "as mandated, are to rapidly move forward in individualized medicine in different ways," says Goetz. "We are doing that by supporting research to the tune of millions of dollars." Goetz did not disclose the full amount of Mayo Clinic research linked to personalized medicine.
"If you look at the healthcare landscape right now, there's a sort of personalized approach that has been going on for decades. We didn't call it personalized," Goetz adds. "With the best data we have now, there is not a smoking gun for what causes cancer. We are left with how do we best understand genetic alterations, and the resistance to our best therapies. We are not going to get rid of the old therapies, but probably will continue them, and understand what are the mechanisms for resistance, and study them in a way it doesn't take 18 years to find an answer."
At the Mayo Clinic Florida and Mayo Clinic Arizona, hospital researchers are examining specific types of cancer and how personalized medicine may make a difference.
Patients enrolled at Mayo Clinic Florida are diagnostic odyssey cases–people whose symptoms are suspected of having an underlying genetic condition or heritable cause but have eluded traditional diagnosis. These are often rare or poorly understood conditions. Hospital officials believe the whole genome sequencing may offer more clues for diagnosis, as well as potential treatment and prevention, Goetz says.
At Mayo Clinic Arizona, researchers have been using whole genome sequencing to look for novel treatments for intractable and incurable cancers. Now, patients who have exhausted traditional treatments will have their tumor genomes sequences to identity pathways to make them suitable targets for therapeutic drugs. Then physicians can identify unusual or experimental chemotherapies, such as drugs that may be usually used for breast cancer, but also may be suited for lung cancer. The tumor genome analysis also can help researchers understand why some tumors respond better than others to chemotherapy, Goetz says.
A significant Mayo Clinic undertaking in personalized medicine includes its Breast Cancer Genome Guided Therapy Study, in which 200 patients have been identified and will participate in a clinical trial examining mutations that would allow some tumors to adapt and thrive during chemotherapy.
The project focuses on women with high-risk cancers. As part of the study, patients are paired with mouse "avatars" that are expected to help doctors identify the best individual treatment, according to Judy C. Boughey, MD, associate professor of surgery at the Mayo Clinic. The patients' tumor tissue will be kept alive by implanting cell lines in immune-compromised mice before and after chemotherapy. The use of the mice will let researchers study the impact of chemotherapy on each patient tumor without risk of harm to the patient.
The study has "real potential to bring individualized medicine to our patients," Boughey says. For patients who have a "higher risk for reoccurrence" of cancer, the project can open the door to "go forward and identify drug development and focus on these patients," she adds.
Patients are increasingly showing willingness to undergo tests to receive advanced experimental treatment in clinical trials, according to a study by the Mayo Clinic and the Translational Genomics Research Institute in Phoenix.
Success key No. 4: Pharmaceutical contracts
For personalized medicine, more hospitals are forming contractual relationships with pharmaceutical companies to develop drugs that may give them an upper hand in the race for improved cancer care.
"We have a long history of working with pharmaceutical companies, over five years," Moffitt's Dalton says. Moffitt has developed a strategic partnership with Merck & Co., which helped underwrite some of the cost of building the infrastructure and has partnered for scientific discovery, Dalton says. By collaborating on a framework with a pharmaceutical company, new drug targets are being developed, he says.
M2Gen, the wholly owned subsidiary of the Moffitt Cancer Center, is supporting the operation of the research initiative, according to the hospital's annual report. M2Gen is partnering with Merck and other pharmaceutical and biotechnology companies to launch clinical trials using the biorepository for data on an IT platform with Oracle.
The Moffitt-Merck research collaboration was formed in December 2006. Funding sources included Hillsborough (Fla.) County, the city of Tampa, and the state of Florida. According to the report, the M2Gen venture is "dedicated to using molecular technology to identify biological markers." Under the plan, M2Gen operations "assist in collecting and processing data, while also carrying out certain monitoring responsibilities."
Without disclosing specific details of the arrangement with the pharmaceutical firm, Dalton adds, "They don't know who the patients are, but they are able to mine the data we are creating and determine new drug targets, then develop drugs effective in patients not responding to new therapy."
Other healthcare enterprises also are working with pharmaceutical companies to develop personalized medicine programs. Earlier this year, the Cancer Treatment Centers of America announced it reached a research collaboration agreement with Merrimack Pharmaceuticals, a Cambridge, Mass., biopharmaceutical company, to better understand cancer on the molecular level and accelerate personalized treatments for the disease. As part of the collaboration, CTCA will provide archived tumor biopsies from its extensive tumor databank and collect tumor samples for analysis.
The collaboration could result in companion diagnostics to guide treatment. Merrimack CEO Robert Mulroy said in a statement that "the collaboration represents the future of individualized treatment, where a hospital and biopharmaceutical company work together on research, which we hope will ultimately result in much better treatment of cancer patients."
The Mayo Clinic also acknowledges the importance of working with pharmaceutical companies for potential personalized medicine drugs. Those discussions are for "early-stage development of drugs, or maybe drugs that haven't been developed yet and we provide a target," says Goetz, of the Mayo Clinic oncology department. "We are looking at collaborating with multiple pharmaceutical companies and an array of partners."
Indeed, pharmaceutical companies are actively pursuing personalized medicine, with as many as half the U.S. drug companies developing personalized medicine programs, according to Christopher-Paul Milne, DVM, MPH, JD, director of research at the Tufts Center for the Study of Drug Development in Boston.
"I haven't heard that companies are backing off their commitments to push forward with personalized medicine, especially as they are increasing their efforts to demonstrate the value of their products compared to competitor products or other therapeutic options," Milne says.
The government also has become deeply involved in promoting personalized medicine, with the Federal Drug Administration coordinating programs for oversight of its research centers to specialize in such programs.
More than 40 years after Nixon's declaration, the White House this year released its national bioeconomy blueprint that laid out strategies in U.S. biotechnology, noting that "advances in recent technologies have increased the momentum of personalized medicine, customized healthcare based on specific genetic or other information of an individual patient."
Reprint HLR0912-7
This article appears in the September 2012 issue of HealthLeaders magazine.
Joe Cantlupe is a senior editor with HealthLeaders Media Online.
