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Thursday, January 22, 2015

 

By Peggy Eastman

 

WASHINGTON—A comprehensive new report from the Institute of Medicine (IOM) calls for creating a culture where sharing data from clinical trials is the norm, and recommends sharing data that support trial results no later than six months after publication. The report was released at a news briefing here.

 

The report, “Sharing Clinical Trial Data: Maximizing Benefits, Minimizing Risks,” also recommends that the full analyzable data set from a clinical trial be shared no later than 18 months after study completion or 30 days after regulatory approval.

 

Twenty-three sponsors supported the new study, including the National Institutes of Health, Food and Drug Administration, pharmaceutical and biotechnology companies and charitable trusts. The IOM is an independent, neutral body whose recommendations carry weight, even though they do not have the force of law. The report recommends that the sponsors convene a multi-stakeholder group to further explore and deliberate on obstacles to clinical trial data sharing.

 

In a related development, the American Society of Clinical Oncology announced its intention to submit a comment letter shortly to NIH regarding two proposals to increase the transparency of clinical trials via information submitted to ClincalTrials.gov, the publicly accessible database operated by the National Library of Medicine, a component of the NIH.

 

“I think this is such an important report,” said IOM President Victor J. Dzau, MD, in introducing the document at the news briefing. Citing the wealth of data now being produced by clinical trials and improvements in the tools used to collect it, Dzau said, “We must be prepared to responsibly respond to these changes.

 

“An open-data movement is really gaining momentum,” he added, noting that sharing trial data in an open-source fashion will strengthen the regulatory science base. But, he noted, “Change is not always easy or comfortable,” and there are challenges to creating a culture of open data sharing in science and medicine – where competition has reigned for years.  

 

‘Big and Difficult’

The Chair of the IOM committee that wrote the report, Bernard Lo, MD, President of the Greenwall Foundation, called the report big and difficult and said there is a strong public interest in releasing and sharing full clinical trial data: “The question is not whether to share but when. We think data sharing should advance the science that is the foundation of medical care.”

 

Lo, a former Professor of Medicine and Director of the Program in Medical Ethics at the University of California, San Francisco, noted that much clinical trial data is never released or published, and stressed that releasing such data in a timely fashion allows other investigators to do confirmatory trials and makes the data available for secondary research – thus strengthening and bolstering the science base.

 

Ideally, data sharing could be used to speed new therapies from bench to bedside, he said: “We think it’s important that there be a pipeline for new drugs.”

 

But Lo noted that “the time point is controversial” as set forth in the new report, and he recognized the need to protect intellectual property and commercially confidential information. Scientists spend years on their work and want credit for their efforts, said Lo and added, “We realize that at this time no committee can settle all the issues related to data sharing.” 

 

Challenges

Challenges to data sharing include:

  • protecting the privacy of clinical trial participants;
  • strengthening the infrastructure for data sharing, since currently there are insufficient platforms to store and manage the breadth of trial data;
  • strengthening the technology for data sharing, since currently data sharing platforms are not consistently discoverable, searchable, or interoperable;
  • training an adequate workforce to manage the operational and technical aspects of data sharing; and
  • creating a sustainable system that distributes costs equitably across both generators and users of data.

 

The Institute of Medicine is not the only body examining issues relating to clinical trial data sharing: The U.S. Department of Health and Human Services (HHS) has issued guidance on methods for de-identification of protected health information in accordance with the Health Insurance Portability and Accountability Act (HIPAA) privacy rule. HHS has also issued guidance on responsible data management in scientific research, including data sharing, through the HHS Office of Research Integrity.

 

Journals

During the question-and-answer part of the news briefing, Lo and committee members addressed the committee’s timeline for release of clinical trial data (presented as a schematic diagram in the report) more specifically. Asked by OT how these recommendations will affect publication of a new study in a professional journal, given the time lag that often attends such publication, committee member Ida Sim, MD, PhD, said: “Journals need to be part of the whole culture of data sharing… We do need a culture of change.” 

 

Some of the new scientists coming into the field are already sharing data, while “for those of us who’ve been around a while, this is a little bit new,” added Sim, Professor of Medicine and Co-Director of Biomedical Informatics of the Clinical and Translational Science Institute at UCSF.

 

The report’s guidelines include a recommendation that journals should “require authors of both primary and secondary analyses of clinical trial data to document that they have submitted a data sharing plan at a site that shares data with and meets the data requirements of the World Health Organization’s International Clinical Trials Registry Platform before enrolling participants,” among others.

 

“We’re trying to be faster on our end,” said Rebecca E. Cooney, PhD, North American Editor of The Lancet, who attended the news briefing. She added of the IOM committee recommendations: “Something like this would actually make our lives easier” because there are standards from the outset. “I think it’s actually a great change,” she said.

 

Participating by telephone, IOM committee member Joanne Waldstreicher, MD, Chief Medical Officer of Johnson & Johnson (a report sponsor), said academic research institutions play a key role in fostering a culture of data sharing. She added that the committee is calling on universities to help support a shift in attitudes and policies, a shift that makes data sharing the norm in science.

 

The committee looked very carefully at current methods of protecting the privacy of study subjects when data are shared, said committee member Deven McGraw, JD, MPH. “De-identification technologies must remain robust,” she emphasized.

 

Negative as well as Positive Data

Data sharing should include data from negative as well as positive trials, said Joel Kupersmith, MD, Adjunct Professor of Medicine at Georgetown University Medical Center, who attended the news briefing. Waldstreicher responded that under the committee’s recommendations and vision for the future, sponsors of trials are encouraged to show whether their studies are positive or negative, and whether the sponsor intends to go forward with a potential therapy.

 

Kristen Cox Santiago, MS, Director of Strategic Initiatives & Outreach for C-Change, asked which of the challenges identified by the committee presents the biggest obstacle to data sharing from clinical trials. Sim answered, “The most effective way to do this is to look at them all together.” 

 

Santiago later told OT that she asked the question because C-Change, whose motto is “collaborating to conquer cancer,” intends to focus on the role of so-called big data in cancer research in 2015.

 

 

Specific Recommendations

The IOM committee’s specific recommendations in the report are as follows:

            1.  Stakeholders in clinical trials should foster a culture in which data is the expected norm. Specifically, at the time of trial registration before the first participant is enrolled, trial sponsors and investigators should have a plan for which data will be shared, when it will be shared, and under what conditions, making the data available publicly at a third-party site that shares data with and meets the data requirements of the World Health Organization’s International Clinical Trials Registry Platform. Investigators and sponsors should design clinical trials and manage trial data with the expectation that data will be shared, and journals should require authors to document that they have submitted a data sharing plan at a site that meets WHO requirements.

            2.  Sponsors and investigators should share the various types of clinical trial data no later than: 12 months after study completion (including adverse event summaries) for summary-level results of clinical trials; 12 months after study completion for lay summaries of results to be made available to trial participants; 18 months after study completion for the full analyzable data set, including the full protocol, any modifications and the final protocol (unless the trial is in support of a regulatory application); and six months after publication for the analytic data set supporting results (including tables and figures). The post-regulatory data package for a newly approved product should be shared 30 days after regulatory approval.

            3.  Holders of clinical trial data should mitigate the risks and enhance the benefits of responsible data sharing by employing data use agreements, designating an independent review panel, including members of the lay public, and making access to clinical trial data transparent. Specifically, they should protect the intellectual property interests of sponsors, give credit to investigators who collected the clinical trial data, and employ techniques for protecting privacy, in addition to de-identification of subjects and data security.          

            4.  The sponsors of this IOM study should take the lead in convening a global multi-stakeholder body to address in an ongoing process the key infrastructure, technological sustainability, and workforce challenges associated with the responsible sharing of clinical trial data.  


Tuesday, January 20, 2015

 

BY PEGGY EASTMAN

 

For the first time, the American Society of Clinical Oncology has named a “cancer advance of the year”—in this case the remarkable improvement in the treatment of chronic lymphocytic leukemia (CLL), which is the most common form of adult leukemia. The announcement, made this morning, was made in the society’s most recent “Clinical Cancer Advances” report, which has now been published annually for 10 years.

 

The report is published online ahead of print in the Journal of Clinical Oncology (doi: 10.1200/JCO.2014.59.9746), on ASCO’s research advocacy website, CancerProgress.Net/CCA, and on Cancer.Net (Cancer.Net/blog/2015-01/cancer-advance-year-transformation-cll-treatment).

 

According to the Leukemia and Lymphoma Society, in 2014 an estimated 15,700 Americans were diagnosed with CLL; most were older (the average age at diagnosis is 70).  These new patients joined an estimated 119,386 Americans who were living with or in remission from CLL as of Jan. 1, 2010.

 

The ASCO report cites four new drugs that have made a major difference for CLL patients:

  • the immunotherapies obinutuzumab and ofatumumab for previously untreated CLL (used in combination with standard chemotherapy); and
  • the molecularly targeted agents ibrutinib and idelalisib for treatment-resistant or relapsed CLL.

“For many older patients, especially, these drugs essentially offer the first chance at effective treatment, since the side effects of earlier options were simply too toxic for many to handle,” said Gregory A. Masters, MD, co-executive editor of the new report, in comments accompanying the publication. The new drugs will fill an enormous need, added Masters, Attending Physician at the Helen F. Graham Cancer Center and Associate Professor at Thomas Jefferson University Medical School.

 

The new treatments, all approved in 2013-14, have fewer adverse effects compared with standard therapy for CLL.

 

‘Stunning New Possibilities’

In his written message introducing the new report, ASCO President Peter Paul Yu, MD, said the four new drugs have brought “stunning new possibilities” to the treatment of patients with CLL. Yu, Director of Cancer Research at the Palo Alto Medical Foundation, noted that “until the past year, many older patients were without treatment options, because existing therapies caused severe, even life-threatening, adverse effects for those who were frail or had other major health problems.”

 

In addition to highlighting one major advance, the new ASCO report is also different from previous reports in that its advances are organized by theme, not by disease areas. So, for example, one section concerns how precision medicine research is bringing new therapies targeting the immune system and cancer cells, while another concerns genomic discoveries and the leads they provide for cancer prevention and therapy.

 

Yu said this has been a “banner year” not just for CLL but for clinical cancer research as a whole. Indeed, in addition to ofatumumab and idelalisib for CLL, the report features five other new anti-cancer therapies approved by the Food and Drug Administration from January 2014 to October 2014. These are:

            1.  Ramucirumab, for advanced gastric or gastroesophageal junction adenocarcinoma that cannot be surgically removed or has metastasized after chemotherapy;

            2.  Slituximab, for multicentric Castleman’s disease;

            3.  Ceritinib, for ALK-positive metastatic non-small cell lung cancer;

            4.  Belinostat, for relapsed or refractory peripheral T-cell lymphoma; and

            5.  Pembrolizumab, for unresectable or metastatic melanoma and disease progression after ipilimumab and, if BRAF V600 mutation is positive, progression after a BRAF inhibitor.

 

The report also points to FDA approvals for the following new uses for existing agents:

            1. Trametinib and dabrafenib in combination to treat unresectable or metastatic melanoma with a BRAF V600E or V600K mutation;

            2.  Ibrutinib for CLL;

            3.  Mercaptopurine as an oral suspension for acute lymphoblastic leukemia (ALL) as part of a combination regimen; and

            4. Bevacizumab for intravenous infusion to treat metastatic cervical cancer, in combination with paclitaxel and cisplatin or paclitaxel and topotecan.

 

Prevention, Screening, Treatment, Patient Care, Quality of Life and Survivorship, and Understanding of Tumor Biology

The ASCO report covers advances in prevention, screening, treatment, patient care, quality of life and survivorship, and understanding tumor biology, highlighting the promise of modern throughput technologies in providing extensive molecular data on cancerous tumors. For example, the report cites two recent studies that have implications for future cancer prevention and therapy:

 

In the first study, investigators “were able to link known cancer triggers, such as tobacco and sun tanning, to specific sets of genetic changes or mutational signatures in tumor tissue,” in the words of the report. In the second study, “similar mutational signatures were sometimes found in entirely different types of cancer.”

 

This finding, the report notes, has major implications for treatment, since it may mean that therapy is more dependent on mutations in a tumor than on the organ in which the tumor arises. So, for instance, this may mean that patients with bladder cancer who have a specific mutational signature found in lung cancer should be treated more like patients with lung cancer than like patients with bladder cancer.

 

The society also looks back at the past decade, reviewing the most significant advances over the decade that the reports have been produced. This year’s document also casts a spotlight on progress in rare cancers, which have often lagged behind progress against the most common cancers.

 

For example, the report highlights early results from a federally funded study indicating that bevacizumab is active against recurrent sex cord-stromal tumors of the ovary, a rare form of ovarian cancer. Bevacizumab, approved for treatment of certain types of colorectal, kidney, lung, and brain cancers, appears to be effective against these rare ovarian tumors by cutting off their blood supply.

 

’10-Year Horizon’

In a section titled “The 10-Year Horizon, the report also looks ahead. This information is particularly intriguing, as it looks at fundamental and translational cancer research findings that may shape the future of cancer care.

 

For example, cancer stem cells are called “the bane of cancer therapy resistance.” Cancer stem cells are thought to be biologically different from “regular” cancer cells in that they can self-renew and generate different cancer cell types, just as normal stem cells can generate different organs and tissues. The report notes that researchers are exploring several strategies to kill biologically different, treatment-resistant cancer stem cells, such as targeting specific molecular pathways (Notch and Hedgehog, for example), proteins on the surface of cancer stem cells and the tumor microenvironment.

 

The report also cites faster, cheaper, and more sophisticated genomics technology, including next-generation sequencing (NGS). Today, the authors note, a person’s whole genome can be sequenced in a few days for $5,000, which is a far cry from the estimated $13 billion and the 13 years it took to complete the Human Genome Project.

 

Such sequencing holds tremendous promise as a diagnostic tool and a way of tailoring treatments to individual patients, the report states. The good news is that smaller NGS machines are already available for use in hospital laboratories, but the report notes that realistically, there are “many technologic, regulatory, ethical, and cost concerns that have to be resolved before these technologies become broadly implemented.”

American Association for Cancer Research President Carlos L. Arteaga, MD, agrees that NGS represents a major advance for the future: “As we move forward, I foresee the increasing use of next-generation sequencing of tumors, which will allow us to dig more deeply into the biology of these cancers,” said Arteaga, Professor of Medicine and Cancer Biology at Vanderbilt-Ingram Cancer Center, in a posting on the AACR web site.

 

“This technology is advancing rapidly, and will allow us to examine more and more genes in a patient’s cancer, and eventually the whole tumor genome.”

 

Also in the future, the ASCO report predicts, are liquid biopsies done from a blood sample rather than a tissue sample--liquid biopsies allow the counting and extraction of circulating tumor cells. Additionally, the report cites the concept of extending liquid biopsies to detecting, capturing, and analyzing circulating tumor DNA (ctDNA) and tumor microRNA, minuscule pieces of the cancer cell’s genetic material that float freely in the bloodstream.

 

Nanomedicine based on nanotechnology is also featured in this section: “Nanotechnology has come a long way in the past couple of decades, and it holds tremendous promise for cancer therapy.” The report notes that the first nanoparticle-based cancer treatment, paclitaxel, was approved by the FDA in 2005 for the treatment of breast cancer.

 

Federal Support Key

While “Clinical Cancer Advances 2015” has a hopeful tone, it is not without a stern warning on the consequences of reducing society’s commitment to federally funded cancer research. In his introductory message, Yu notes that nearly a third of the studies featured in the new report were supported by federal research dollars. He states that “federal investment in research has stagnated over the past 10 years, resulting in a 23 percent loss in purchasing power for the National Institutes of Health.

 

“In practical terms, this means that promising research is going unfunded, new studies are being scaled back, fewer patients have the opportunity to participate in clinical trials, and future meaningful advances against cancer may be few and far between--unless our nation renews its commitment to fighting cancer.” 

 

ASCO Chief Medical Officer Richard L. Schilsky, MD, expressed similar concerns: “The U.S. federal cancer research enterprise faces crucial funding challenges that threaten the pace of research progress. Now is the time to increase our nation’s investment in cancer research to ensure that we can build on these advances well into the future.”  

 

ASCO has called upon Congress to increase the federal investment in medical research innovation.

 

The report cites the following major advances made possible by federal research dollars:

  • Adding generic chemotherapy to standard advanced prostate cancer treatment, which has increased survival;
  • Adding a generic, low-cost hormone treatment to standard chemotherapy to help preserve the fertility and extend the lives of young women with breast cancer undergoing chemotherapy;
  • Combining standard radiation therapy with chemotherapy to add years of life to patients with low-grade glioma;
  • Identifying ways to maximize benefits and reduce potential risks from low-dose computed tomography (CT) lung cancer screening; and
  • Using new molecularly targeted drugs to help overcome treatment resistance in lung cancer.

Coauthors

In addition to Gregory Masters, the other coauthors of the report are Lada Krilov (corresponding author), Howard H. Bailey, Marcia S. Brose, Harold Burstein, Lisa R. Diller, Don S. Dizon, Howard A. Fine, Gregory P. Kalemkerian, Mark Moasser, Michael N. Neuss, Steven J. O'Day, Olatoyosi Odenike, Charles J. Ryan, Richard L. Schilsky, Gary K. Schwartz, Alan P. Venook, Sandra L. Wong, and Jyoti D. Patel, the other co-executive editor of the report.


Tuesday, January 13, 2015

 

On January 5, the College of American Pathologists introduced a new logo (shown above), the most recent phase of the organization’s branding redesign (which also included a website redesign that was launched in December). Over the coming year, all materials that reach members, other physicians, health care executives, policy makers, patients, and the public will be updated to include the new look.

 

“We are reinvigorating the CAP brand, including the logo, as we continue to evolve with the changing health care marketplace and changing technologies,” CAP CEO, Charles Roussel, said in an email. “Because health care reform, financial challenges, and patient satisfaction remain top concerns in health care, like all health care organizations, the CAP and its members must adapt and make our value known.

 

“With a history dating back more than 60 years, we wanted to redefine who we are to better reflect what we do now.”

 

 

Above: Former CAP Logo

 

The new branding, including the logo and the website redesign, has been in the works for more than two years, Roussel noted. “We carefully examined our relationships with key audiences, such as oncologists, and the value pathologists offer—i.e., working together to improve the clinical effectiveness of how oncologists care for their patients while making their jobs more efficient throughout the continuum of care.”

 

Input about the new design was collected from CAP members, staff, oncologists, primary care physicians, health care administrators, and researchers. The final selection was based on the feedback from all of those audiences and made by the CAP Board of Governors.

 

In a statement on the CAP website, the organization’s president, Gene N. Herbek, MD, FACP, said: “We’re proud to introduce a new logo. … It’s dynamic while representing the promise that a combined strength benefits patients, physicians, health care systems, and the public because people are healthier when cared for by pathology and laboratory medicine.”


Monday, January 12, 2015

 

BY MARK FUERST

 

Health care professionals are generally optimistic about the applications of personalized medicine in oncology and say that successful implementation of precision oncology depends on the readiness of health care practitioners to adopt the technology, along with the availability of the needed infrastructures, according to the results of a new survey.

 

“The findings may surprise you, as many believe that advancing science is only the first step,” said Susan Garfield, DrPH, Senior Vice President of GfK, the research organization that conducted the Novartis-sponsored survey of approximately 230 health care professionals--more than half of them oncologists, hematologists, surgeons, and gynecologists.

 

“Practicing oncologists need to think about using precision oncology for their patients who do not have any standard therapies available,” said Lee Schwartzberg, MD, Chief of the Division of Hematology Oncology at the University of Tennessee and Medical Director at the West Clinic in Memphis, Tennessee. “Get them into trials to give them access to drugs. Make the testing operationally useful so you can use precision oncology for your patients.”

 

In an interview, Schwartzberg said he has become excited about the promise of using molecular alterations to make treatment decisions: “We have tangible results in terms of more specifically targeted drugs and companion diagnostics to pick the right therapy, and an increasing awareness of what happens after resistance occurs.”

 

Some cancer experts, though, are less sanguine about the promise of precision oncology. “The reality is that there are a few wonderful examples of precision medicine, but they are few and far between, and they are very expensive and often overhyped,” said Leonard Saltz, MD, Professor of Medicine at Weill Cornell Medical College and Chief of the Gastrointestinal Oncology Service at Memorial Sloan-Kettering Cancer Center.

 

“Add to all this that ‘precision’ or ‘targeted’ medicines have some awfully nasty side effects. The idea that we would make cancer drugs similar in toxicity to other medicines used to treat other diseases is thus far just a fantasy. For most people in most common diseases, precision medicine is not a step forward.”   

 

4 Key Areas of Focus

In the survey, the respondents identified four keys areas of focus for successful implementation of precision oncology: collaboration, professional capabilities, care processes, and systems and infrastructure. The consensus was that a new level of collaboration among oncology care professionals and across health care systems is necessary to enable effective patient care.

 

“Personalized medicine will place new demands on health care professionals to understand and interpret data and manage increasingly complex disease patterns and treatment strategies,” Garfield said. “Process improvements need to happen in parallel with scientific advancements to deliver personalized care. Funding, reimbursement and information technology systems must adapt to enable patient access to innovation.”

 

Oncologists will need to expand their knowledge base to include the increasing number of new precision medicines, Schwartzberg added. “We need to become experts in multiple diseases and understand their biology if we want to use precision oncology to the maximum. There is data emerging almost every day. Either we become more subspecialized or gain access to resources and experts to interpret the data.”

 

He acknowledged that it may be difficult for an oncologist to see the same volume of patients when prescribing precision medicines.

 

One-third of health care professionals interviewed for the survey said they believed that communication and collaboration regarding personalized medicine in oncology care currently is effective and efficient. American respondents were more skeptical: Only one-quarter of those in the U.S. said they feel that today’s precision oncology is working well; in comparison, two-thirds of those in Italy do.

 

The promise of precision medicine is “the matching of effective therapies to specific cancers based on molecular drivers, and as a result maximization of benefit and a minimization of toxicities,” Saltz explained. “Everyone still harkens back to Gleevec [imatinib], a drug that is so old it is about to go off patent. It works very well on a rare disease, chronic myelogenous leukemia, because CML happens only when one particular molecular event happens. That is why it is so rare.”

 

Schwartzberg agrees that in solid tumors, it is unlikely researchers will find another success story like imatinib. “In CML, there is one alteration that doesn’t change, and there are no escape pathways for the mutation, but that doesn’t mean we can’t find multiple ways to target solid tumors.”

 

There is a rationale for combination therapies. Cancer can develop through multiple abnormal pathways and at multiple points within a single pathway. Some “smart cancers” can mutate and create “escape routes” through new pathways, which can lead to drug resistance. A strategy of combination targeted therapies may block multiple targets, stopping escape routes, preventing resistance, and improving outcomes.  

 

Real Benefits

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is another positive example, Saltz said, and one “where we can say that a targeted approach has made a real, clinically meaningful difference.”

 

Schwartzberg noted that HER2 amplifications or mutations are found in a variety of cancers at a low frequency beyond breast cancer.

 

Another pathway under examination is the translocation of the ALK (anaplastic lymphoma receptor tyrosine kinase) gene. The ALK alteration has been associated with anaplastic large cell lymphoma, non-small cell lung cancer (NSCLC), breast cancer, and colorectal cancer. For example, NSCLC patients who have a translocation in the ALK gene or in the ROS gene respond to crizotinib, the first-generation ALK inhibitor, and there are several other drugs in development now that are even more potent for this particular alteration.

 

But Saltz noted recent research showing that crizotinib is not cost-effective for ALK-mutated lung cancer. “And don’t forget that ALK-mutated lung cancer is only in the low single digit percentages of all lung cancers,” he continued.

 

“Epithelial growth factor receptor-mutated lung cancer was already being treated with Tarceva, along with everyone else with lung cancer, before we finally got people to stop prescribing it for all patients, and now we give it to only about one in five patients who have an EGFR mutation,” he said.

 

“KRAS mutations are found in almost one quarter of lung cancer patients, but nothing targeted will work for them. Remember, before precision medicine, lung cancer was the number one cause of cancer death. We should not lose sight of the fact that it still is.”

 

As for colorectal cancer, “we have found that you can now use all-RAS genotyping to exclude more than half of the patients from treatment with cetuximab or panitumumab,” Saltz said. “The ‘precision’ part is just saving the money and expense of not treating more than half the people with an agent that will not help.”

 

Schwartzberg, however, says that he sees opportunities with precision treatments--in particular using selective BRAF and selective MAPK kinase (MEK) inhibitors now on the market.

 

“The B-raf gene mutation is found in lung, gastrointestinal, endocrine, and colon cancers. Clearly, it is a common pathway abnormality. We now see critical oncogenes changes in terms of HER2 mutations and more downstream alterations, such as in BRAF and MEK,” he said.

 

Diagnostics

Another essential part of precision oncology is diagnostics, and one third of cancer medicines in late-stage development currently use a diagnostic test to identify which patients are likely to respond.

 

Schwartzberg said: “I don’t use tests to make initial treatment decisions other than where there is an approved drug. This is critical in NSCLC, where up to one-third of patients may have upfront mutations. If I can’t use precision medicine in first-line therapy, then I want to be prepared for the next line of therapy.”

 

Challenges Ahead

Although virtually all (98%) the respondents interviewed for the survey said they expected that personalized medicine will have a positive impact on oncology care, 70 percent agreed that there are significant challenges to the implementation. Approximately 90 percent said they expect companion diagnostics to provide at least the same or greater clinical value for oncology care in the next three to four years.

 

One challenge is acquiring enough tissue for appropriate testing. “Technology is better, but we still need tumor tissue for testing,” Schwartzberg said. “In some cancers, that is not available, and we may require an additional biopsy.” He said he has high hopes for a liquid biopsy approach that probes a patient’s blood using circulating DNA or tumor cells to look for specific mutations. The technology is available now, but requires additional validation.

 

There are also issues with testing. “We need to pick the right test and work with companies who have experience with next-generation sequencing. The market has to be defined. We also need to coordinate with the laboratory and pathologist. Some tests take time--up to several weeks—but many cancer patients can’t wait that long for a new therapy,” Schwartzberg said.

 

Then there is the matter of interpretation: “What do the tests mean? Labs are getting better at providing annotated reports to help oncologists interpret data. The results are still complex and many clinicians do not understand the significance. Using the information to make treatment decisions can be difficult for a busy practitioner who may not have the time or resources to fully interpret the reports,” he said, adding that many laboratories now provide access to a molecular geneticist.

 

In his hospital, “we have a clinical genomics tumor board that meets every week to review all results sent out by our physicians. We help them interpret the results and send them our group’s recommendations.”

 

Reimbursements

The survey respondents cited education as a necessity to achieve full implementation of personalized medicine. However, some of them also see it as an impediment to expanded use. Both reimbursement and funding are also necessary.

 

“Reimbursement is driven by value,” Garfield said. “There has been a relatively positive response to personalized medicine because it is a cost-effective approach to care. Payers around the world have been receptive to personalized oncology.”

 

“We can do broader molecular analyses now, and insurance companies are becoming better at reimbursing for them,” Schwartzberg said. “This makes it easier from both the patient and provider perspective. Panels are giving us actionable mutations, and this gives us more latitude to what we do. We can find out exactly what is happening to the patient beyond diagnostics.”

 

Saltz pointed out, however, that for now, the main source of information about personalized medicine comes from the burgeoning industry of expensive molecular analyses, as well as from the pharmaceutical industry.

 

Short-lived Results

The biggest flaw in precision medicine, Saltz said, is that “the benefits thus far tend to be very short-lived before other mutations emerge and disease control is lost. Cure is virtually unheard of. Median disease control is usually measured in months, and rarely approaches anything close to a year. As such, patients are too frequently experiencing an ‘is-that-all-there-is’ phenomenon. When they get precision medicine, all too soon they are looking into the abyss again.”

 

Schwartzberg agreed, but said progress is starting to accelerate: “There is a lot of hype or enthusiasm with any new modality. I was skeptical until a year ago. Anything with life and death, people want to believe. A lot of money has been spent on genomics that has not translated into many drugs yet.

 

“We have only done genomics for a few years, so our understanding of the range of mutations and alterations is incomplete,” he continued. “It has been only about a dozen years since the human genome was sequenced. In the last few years, multiple molecularly targeted therapies have been developed. Do they cure cancer? No, they target alterations, and provide incremental clinical benefit.”

 

He said he believes multiple targets are probably needed for more meaningful benefit, and cites the example of combined treatment with dabrafenib, a selective BRAF inhibitor, and trametinib, a selective MEK inhibitor, in the treatment of metastatic melanoma. “The weight of evidence is moving away from doubters. Melanoma, a disease that typical was fatal within months, now has a median progression-free survival of one year or more. That’s meaningful benefit,” he said.

 

Schwartzberg acknowledged that there have been no inroads made in prevention strategies. “We need to understand the molecular alterations that occur in the run-up to invasive cancer. If a target is identified, we may be able to intervene before disease develops. That might, in the long run, be where precision medicine has its greatest impact.”

 

‘Time to Get on Board’

The time to be skeptical about precision medicine is rapidly fading, Schwartzberg maintained. “It’s time to get on board. Not everyone needs to embrace precision oncology, and not every patient needs whole exome sequencing. But it is the future. More therapies will be targeted.

 

“After all, chemotherapy targets DNA or microtubular damage. Clearly, it targets molecular events. We didn’t have the tools to understand that in the past, but we do now.”

 

The continuing challenge for oncologists will be to keep up with the ever-growing amounts of information and choose the right treatment. “The clinical trial system doesn’t allow drugs to be tested quickly,” Schwartzberg said. “Everyone will test drugs on different patients. I strongly encourage an ‘n of 1’ data or registry approach. We will miss a valuable opportunity if we don’t aggregate that data. If we do, the promise of precision oncology will be realized faster.”


Sunday, January 11, 2015
 

BY MARY BROPHY MARCUS

 

The American Society of Clinical Oncology and the College of American Pathologists have together announced a new partnership, with the goal of improving the development, application, interpretation, and dissemination of pathology tests so that patients and their oncologists can obtain the most accurate diagnoses, so that optimal treatments can be individually tailored.

 

"It is our hope that all oncologists and those pathologists involved in cancer diagnosis and treatment will benefit from this collaboration that will stimulate and support many collaborative educational programs," said ASCO Chief Medical Officer Richard L. Schilsky, MD, FACP, FASCO, interviewed via email.

 

Schilsky noted that ASCO and CAP have a history of successful collaboration, including the development of joint guidelines on the use of important biomarker tests such as those for HER2 and hormone receptors in breast cancer (OT 11/10/13 issue).

 

"With the rapid growth in precision medicine in oncology and the increasing reliance on molecular diagnostics to select and monitor treatment, ASCO and CAP felt that closer collaboration was important to insure that cancer patients receive high-quality care," he explained.

 

CAP President Gene N. Herbek, MD, FCAP, explained that CAP was formed over 50 years ago with the aim of improving the quality of laboratory medicine and that the new partnership is a natural extension of the relationship that the two groups have been building: "As a pathologist, I work every day with oncologists, either in person or by phone. One of the specialty groups who understand pathologists more than most are oncologists, and they rely on our diagnoses of cancers to be accurate. These tests are critical for treatment. Oncologists needed to be assured that our pathologists in labs around the country are all on equal footing—that all results will be the same as is humanly and scientifically possible."

 

Herbek said the new alliance "elevates the partnership"— that while there are many oncologists and pathologists who know about the collaborative work between the two groups, thousands probably weren't aware of the working relationship until the partnership was announced in December.

 

"When we announced that we want to work together and that this is what we've done and are going to do to improve patient care, it helps our members and patient advocacy groups understand better how we're working together. We need to be very clear about our advocacy efforts so that we can take messages together to the Hill in D.C. and get our senators and representatives educated on what we're doing," he said. "We want to work together with ASCO to really formalize that. It helps move agendas ahead for our patients more effectively."

 

Coming Projects

Some of the projects lined up that will merge the strengths and skills of both organizations include an expansion of ongoing joint guideline development on molecular testing for cancer and the development of point-of-care guidance statements regarding the appropriate molecular work-up of newly diagnosed patients. Plans also involve the launch of a multi-disciplinary, virtual molecular tumor board and planning a joint workshop on cancer diagnostic services in developing countries.

 

"We’ve got a lot of info that we want to get to the practicing pathologists and oncologists who can use it to affect patient care. Right now, a lot of our data is not structured. We're not able to transmit it in a quick, accurate way. So we are working with ASCO on how to standardize that data. We are working very hard on developing standards and guidelines for genomic testing so that we can feel we've done our job, our due diligence, and make sure this is being done for the right reasons."

 

He said another benefit of the ASCO-CAP alliance is that it attracts other organizations that may not have previously been interested in working together--"It adds credibility and enthusiasm, and resources to pay for meetings—it gets people there and it gets work done.”

 

Saranya Chumsri, MD, a breast cancer specialist at the Mayo Clinic in Jacksonville, Florida, said the new partnership is coming at a good time.

 

"The partnership is very important, especially in our field of breast cancer oncology because there are a lot of integrated molecular biomarkers that we use to choose which targeted therapy a patient will benefit from. The FDA is now starting to approve new drugs in combination with the companion diagnostic tests now.

 

"Working together between pathologists and oncologists is crucial to be able to identify the correct population that will benefit from certain targeted treatments," Chumsri said.

 

Schilsky added: "The ultimate goal of this collaboration is to benefit patients, of course, not oncologists, by insuring that each patient has access to high quality, evidence-based precision medicine services."