3 Questions on…
Answers straight from the experts on the latest news and topics in oncology
Wednesday, December 10, 2014
With TATIANA M. PROWELL, MD, Breast Cancer Scientific Lead of the FDA’s Division of Oncology Products 1, and LAURA J. VAN ‘T VEER, PHD, Director of Applied Genomics at UCSF Helen Diller Family Comprehensive Cancer Center
SAN ANTONIO—There are certainly opportunities—some already underway—for successful registration of novel-novel biomarker-specific drug combinations and novel companion diagnostics for specific subsets of patients with breast cancer, Laura J. van’t Veer, PhD, of UCSF’s Helen Diller Family Comprehensive Cancer Center, said in an interview after moderating a session on the topic here at the 2014 San Antonio Breast Cancer Symposium. But, a key point [Ed: and challenge!], she said: “To make it all really work, we need more collaboration across countries—and across continents—to actually provide the regulatory path for drug approvals.”
LAURA J. VAN’T VEER, PHD
Van’t Veer serves as Professor of Laboratory Medicine, Angela and Shu Kai Chan Endowed Chair in Cancer Research, Director of Applied Genomics, and Program Leader of Breast Oncology all at UCSF HDFCCC. And the panel she led also included Tatiana Prowell, MD, Breast Cancer Scientific Lead in the U.S. Food and Drug Administration’s Division of Oncology Products 1 and Assistant Professor of Oncology in the Breast Cancer Program at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, as well as Jan H.M. Schellens, MD, PhD, of The Netherlands Cancer Institute, providing an international perspective on the topic, and Eric H. Rubin, MD, of Merck & Co., providing the pharmaceutical perspective.
In an interview after the session, Prowell and van’t Veer summarized the key messages discussed and why collaborations—both domestic and internationally—are so important. They also commented on whether (and how) such cooperation is possible.
1. First, why are biomarker-specific drugs relevant in breast cancer—and important?
Prowell: “Despite success in certain disease subsets—for example HER2 positive breast cancer—we should not assume ‘problem solved.’ Clearly there are subsets of patients for whom current treatments don’t work, or they don’t work very long. It’s very important for us not to get complacent.
TATIANA M. PROWELL, MD
“As we gain a better understanding of biomarkers and more widespread use of platforms that can test for multiple biomarkers efficiently, we’re likely to see more progress for those very small subsets of patients who may constitute only one or two percent of the overall drug population. Those populations have the opportunity to benefit greatly if an appropriately targeted treatment is found.
“For example in lung cancer look at crizotinib, which for the four percent (or so) of patients who have an ALK-positive lung cancer—and likewise for the only one or two percent of lung cancer who have ROS1-rearranged lung cancer—that drug has quite a high response rate. So I think it’s important for us not to get complacent in breast cancer subtypes where it seems like we’ve made a great deal of progress.”
2. The session was about international collaborations. Why is that cooperation such a big part of getting these drugs developed?
van’t Veer: “I have spent most of my career in the Netherlands, but have now moved the U.S. to San Francisco—so I sort of understand both worlds. What I’ve been observing over the last year and a half is that the global collaboration is taking off immensely because everybody understands that if you screen 10,000 breast cancer patients, you’ll find 400 with a particular characteristic to be able to put in a trial. No one institution will be able to do that. So collaboration is the only way to move this forward, particularly in breast cancer where biomarker subtypes become very small groups—ER-positive, HER2-positive, HER2-negative, and all the subgroups under those.”
P: “We really need to do this globally. Even if you had unlimited resources, it’s just impractical for multiple different groups to be screening 10,000 patients simultaneously over and over. For example, you may have five clinical trials using anti-PD1 or anti-PDL1 agents at a given institution and patients are being individually screened for each trial. Reducing redundancy—the need to do so—is a key message that should come away from this session, not only from country to country, but also company to company.”
3. Is that type of global cooperation feasible? Who is responsible? What are some of the next steps?
P: “What everyone would like to see accomplished, whether they are patients, clinicians, or a pharmaceutical company—we all want better drugs for patients. People may come at it from a different angle—the patient wants access to more treatment options or more effective or less toxic therapy. Clinicians want a longer menu of options they can offer to patients. Pharma is looking to capitalize on the R&D dollars that they put in and make a profit. The bottom line is that in order for any of those things to happen, you need the drug to get approved. So I think regulators are in a unique position to bring everyone to the table. And increasingly I think our FDA Office of Oncology and Hematology Products is taking a very much more proactive role than was the case certainly even five or ten years ago.
“One critical step: patients and clinicians should be aware that it is possible for patients to access investigational agents outside of a trial—both in the U.S. and abroad. There is a relatively straightforward process to do this and the FDA is looking to streamline that process even more so that we increase patient access to compassionate use programs and ensure greater levels of equity in terms of patients who are able to access those drugs in that setting.
“Another opportunity [in addition to streamlining that process of accessing compassionate use programs] would be requiring clinicians to report how those patients [in those programs] did in a public fashion. We have so much data that gets collected that never gets reported or never gets shared or doesn’t get shared broadly enough—and that’s just a lost opportunity. We need to make full use of the data that we have.”
Wednesday, November 12, 2014
With NANDITA KHERA, MD, MPH, Assistant Professor of Medicine in Hematology/Oncology at Mayo Clinic
“I suspect I ought to ask all patients about financial vulnerabilities. After all, shouldn’t it be part of my full review of symptoms? Maybe it is not quite in the same league as shortness of breath, fevers, new neurologic symptoms, or fatigue. Or is it?”
Nandita Khera, MD, MPH—Assistant Professor of Medicine in Hematology/Oncology at Mayo Clinic—poses the question in a recent Journal of Clinical Oncology Art of Oncology article (JCO 2014;32:3337-3338). And in the article’s 11 succinct paragraphs, Khera makes the argument, it might just be.
Khera defines “financial toxicity” as “adverse economic consequences resulting from medical treatment.” She says that financial toxicity—similar to medical toxicity—can lead to treatment nonadherence and lifestyle changes for patients that impact quality of life and increase morbidity and mortality.
Others have suggested solutions could involve government playing a bigger role to rein in costs (OT 11/10/14 issue). But, Khera’s proposes that physicians themselves also need to play a bigger role in being aware of patients’ financial vulnerabilities in order to be aware of how much “financial toxicity” is being caused by those patients’ treatments.
In a phone interview, Khera elaborated on one solution—a standardized financial toxicity scoring system—and why it could be beneficial for patients and physicians.
1. Why do oncologists—and all physicians—need to be aware of the financial toxicities of treatments and how those toxicities affect the patients they treat?
“As physicians, we have to remember, especially as we continue from first-line treatment to second-line treatment to third-line treatment, there are economic consequences. Especially if patients are underinsured or their coverage is not great, they may accumulate a lot of debt and financial burden that can impact their lifestyle—or even their ability to continue their treatment. Both the patient and the physician have to remember that even in the face of a life-threatening illness, you still have to think about those things.
“We’re finding otherwise, that as treatment moves forward, patients will ultimately come and say, ‘I will not take this treatment because I will have to sell my house or do something very catastrophic to be able to do that.’
“In order to not get to that point, I think it is important that we start talking about it. It’s the elephant in the room, but somebody needs to talk about it.”
2. You suggest a “Grading Criteria” or standardized scoring system could help—how does it work?
“It’s a tool that makes it easier for the oncologist to think about financial toxicity and creates a language so we feel comfortable communicating with each other. It’s a system to screen patients and identify who may be at risk for catastrophic financial outcomes as a result of their cancer diagnosis.
“Grade one is lifestyle changes—such as not being able to afford routine expenses. And if patients are struggling with grade one financial toxicities, unless something is done they will likely progress to grade three or grade four where we are going to be dealing with much more severe outcomes—and potentially progression of the patients’ tumors if they cannot continue treatment.
“Once you identify that the patient is having financial difficulties due to the cost of their treatments, at that point the physician can refer them to social services or other resources, such as drug assistance programs.
“The grading system helps address potential financial toxicities as early as possible.”
3. What are the barriers to implementing a system like this one?
“One barrier is attitudes. As physicians we need to see the broad perspective that we do have some responsibility toward patients’ financial well-beings.
“Second is the knowledge barrier. When we order treatments and tests, a lot of physicians don’t know or are not sure what it would cost or what the cost would be for the patient. That can be hard because there is a lot of variability, but even if physicians were more aware of some of the top costs that burden their patients—that would be important in helping overcome that barrier.”
Thursday, September 11, 2014
With LLS’s New President and CEO LOUIS J. DEGENNARO, PHD
Louis J. DeGennaro, PhD, earlier this week became President and Chief Executive Officer of The Leukemia and Lymphoma Society after serving in roles that spanned from academic centers to the private sector to the federal government. But he said new advances in blood cancer research make now an exciting time to be a part of advocacy on behalf of the cause: “The opportunity to defeat blood cancer has never been greater,” he noted.
DeGennaro has served as interim President and CEO of LLS since February, having served on the Society’s leadership team since 2005. He was named LLS Chief Mission Officer in 2009, in which role he played a key role in setting the society’s cures and access agenda, as well as developing the Therapy Acceleration Program, a venture philanthropy endeavor that defined the role of non-profit organizations in supporting drug discovery and development with the biotechnology industry.
Prior to joining LLS, DeGennaro’s experience included: being group leader of the Max Planck Institute in Munich, Germany; serving as Associate Professor of Neurology and Cell Biology at the University of Massachusetts Medical School; serving as Senior Director of Molecular Genetics at Wyeth Pharmaceuticals; serving as Executive Vice President for Research and Development at SynX Pharma, Inc.; serving as Research Manager at Streck, Inc.; and serving as a member of the National Center for Advancing Translational Sciences Advisory Council and the Cures Acceleration Network Review Board at the National Institutes of Health.
After his myriad experiences in health care, we asked DeGennaro what’s exciting about this new role ahead.
1. After experience in the private sector, academia, and government, what makes you excited about this new role—and how do those experiences give you a unique perspective?
“My time in academia taught me what excellent science looks like; my time in big pharma and biotech taught me the challenges of product development; and my time here at LLS has taught me the value of the patient perspective. Together, these lessons will help me guide LLS to achieve its mission of finding cures and making certain that patients have access to life-saving treatments.
“Nearly 40 percent of cancer drugs newly approved by the FDA since the year 2000 were approved first for a blood cancer. With its research funding, LLS is paving the super highway to cancer cures. The application of genomic technology is leading to a growing fundamental understanding of the driver mutations in the hematological malignancies—and that, coupled with robust drug discovery efforts underway by the pharmaceutical industry, paints a hopeful future for new blood cancer treatments.”
2. Which advances in the field would you say you are most excited about?
“In research, I’m most excited about recent advances in immunotherapy, especially: CAR T therapy which was pioneered for the treatment of leukemia at the University of Pennsylvania with $20 million in funding from LLS over more than 15 years: and new targeted therapies like the recent approval of kinase inhibitors for the treatment of chronic lymphocytic leukemia and other B-cell malignancies.
“From an advocacy perspective, we now have an opportunity to develop a nationwide network of patient and volunteer advocates who can bring greater visibility to access issues, including network adequacy and patient cost sharing.”
3. So, what would you say are your goals being President and CEO of an advocacy agency that raises upwards of $300 million to support this cause?
“Our immediate goals are to continue to provide support for patients and identify and fund leading-edge blood cancer research in academia and in the private sector while providing our patients and volunteers with a powerful voice to advocate for better access to quality care. Our long-term goal: cure the blood cancers and put ourselves out of business!”
Thursday, August 07, 2014
With RICHARD L. SCHILSKY, MD, FACP, FASCO, Chief Medical Officer of the American Society of Clinical Oncology
One of the biggest challenges to making personalized cancer care a reality is understanding the potential of targeted drugs outside of their approved indications, Richard L. Schilsky, MD, FASCO, Chief Medical Officer of the American Society of Clinical Oncology, said in a phone interview. He explained the key components of a new ASCO initiative to do just that.
“It’s becoming more and more common to recommend molecular profiling — particularly for patients who have advanced cancer or patients who’ve exhausted all standard treatment options — to determine whether or not those results might suggest a course of therapy for the patient to try,” he said. “But many of those drugs would have to be used off-label, or would only be available in a clinical trial. The problem becomes — how does the patient get access to the drug? And, even if the doctor can get access to the drug and treat the patient, the rest of the medical community has no way of understanding whether that particular approach actually worked in that patient with those characteristics or not.”
The program proposed by ASCO — and now currently being developed by a steering committee — would capture data from real world clinical use of those drugs, and at the same time create incentives that would facilitate easier patient and physician access to those drugs.
“The point is to try to solve how to simplify access to the drug, and also how to learn from the experience of using the drug off-label so that ultimately we can gain more information about whether those approaches are worthwhile to pursue or not,” Schilsky said.
He presented the idea at an American Cancer Society Cancer Action Network forum in April (OT 6/25/14 issue), and he said ASCO plans to launch the program early next year. (The program has not been formally named but is being referred to as the national access program.) Schilsky also outlined the program in a recent Nature Reviews Clinical Oncology Perspectives article (2014;11:432-438).
He spoke to OT about how and why this initiative would lead to better cancer care.
1. How would the program work?
“The program would make drugs available to patients who are willing to enroll in a prospective observational registry study. The patients would need to be enrolled in a protocol that would be similar to a clinical trial — having both eligibility and exclusion criteria, though fairly liberal — and would need to consent to have their outcomes collected so that data could be incorporated into a registry. And, we hope to enlist the interest and support of a number of pharmaceutical companies who would be willing to make some of their marketed, targeted anticancer drugs available at little or no cost to patients through this program — similar to the way they might make drugs available for an expanded access program
“The doctor treating the patient — if they believe that a molecular profiling test is medically appropriate — would have such a test performed (by whatever mechanism they would order such a test). And after reviewing results would determine whether or not one of the drugs that’s available through this program is a good match for the molecular profile of the patient’s tumor and might be a good treatment option. And we intend to include in the protocol some of the criteria that might be used to select a drug to use against a particular mutation site.
“The doctor would then submit the proposed treatment plan to an honest broker — an independent expert group who would review the clinical circumstances of the patient — review the molecular profiling test results, and review the proposed treatment plan offered by the physician to validate that it’s a reasonable approach for this particular patient.
“Once validated, the drug would then be made available to the patient (at no cost to the patient), and the doctor would be obligated to capture the key patient outcomes, both toxicity and efficacy, in the registry.”
2. And the benefits are…
“The basic premise is there are incentives for all the players to participate in a program like this one, which fundamentally provides a vehicle for capturing of good quality, real-world observational data that we can all learn a lot from — that we are not currently able to learn from the off-label prescribing of these drugs.
“Over time we could imagine accumulating lots of data — from hundreds or thousands of patients — on the off-label use of targeted drugs under well-defined circumstances, where we know the characteristics of the patient, the results of the molecular profiling test, the specific treatment that’s been given, and the outcomes for the patient. And then we would share that information broadly with all the participants in the program, and then over time broadly with all of the medical community.
“The patients benefit by having easier access to drugs that they are predicted to benefit from based on molecular profiling test results. The doctors benefit by getting easier access to these treatments. And ultimately the drug companies and the insurance companies benefit by learning a lot about the way in which these drugs are performing in these off-label indications — that information might influence their decision to develop a formal clinical trial, test a promising new lead, or potentially change direction — stop planning for a clinical trial that they were contemplating if it turns out that the real world data does not support it.”
3. What are the next steps to implement a system like this — and potential barriers?
“ASCO will organize the operational aspects of this, which we’re writing a protocol for — and ASCO will ultimately keep the database for the registry. ASCO will also develop all the mechanisms for sharing the data. We’re on a timeline to launch this program early next year.
“I’ve talked to representatives from all the stakeholder groups — doctors, insurance companies, patients, regulatory agencies — and everybody is intrigued by the concept here. Everybody sees its potential value; and essentially all the stakeholders have indicated a willingness to try to work toward making this a reality.
“I would say that the single biggest issue that’s been raised is whether or not the data that would be collected in a project like this is actually of sufficient quality to be useful by all the stakeholders — that this real world observational data can actually enable a regulatory agency or a payer or even a clinical group to make decisions that they have to make — but we won’t know until the data comes in.”
Tuesday, July 08, 2014
With ELIZABETH SMITH, PHD, Professor in Social & Behavioral Sciences in the School of Nursing, University of California, San Francisco
Tobacco use by military personnel is harmful to individuals, it’s harmful to the institution, and there’s no reason to continue supporting or even allowing it — was the argument Elizabeth Smith, PhD, and six co-authors made in a recent Perspective article in the New England Journal of Medicine (DOI: 10.1056/NEJMp1405976).
“People in the military are trying to implement these policies. And it’s really important that they get support from people involved in public health — doctors, nurses, and advocates, including people concerned about cancer,” Smith explained in an interview with OT. Here’s more on why she’s focusing her attention on this issue now…
1. The health risks associated with tobacco are well-known — why is NOW the right time to restrict tobacco use in the military?
“It’s been a good time for a long time. And the military has tried to do a lot of things over the past 20 years, but often Congress has prevented them from implementing strong tobacco control. For example, the Secretary of the Navy Ray Mabus wants to end tobacco sales on navy installations, but the House Armed Services Committee has put an amendment into the defense authorization bill that would prevent him from doing that.
“And that’s where the problem has been for a long time — in Congress, where the tobacco industry has a lot of influence. So public health advocates really need to step up and support the military’s effort to improve the health of the personnel.
“Right now is a good time [to enact this policy] partly because the support from the higher leadership does seem to be there — not only from the Secretary of the Navy, but also from the Secretary of Defense — and also because we’re having a drawdown of our military as forces pull out of combat. Personnel are going to be reduced, so now is a good time to tighten rules and restrict membership.”
2. Is there a precedent to restrict tobacco use in the military? What are the arguments AGAINST restricting its use by the military?
“Yes. Most fire departments do not allow their personnel to smoke because of the health consequences, which is a precedent for restricting tobacco use. It’s never been declared a right.
“It’s never been determined to be a right by any court and smokers are not a protected class. And, many of the rights of military personnel are curtailed in the name of good discipline or good health. Using tobacco is certainly not a benefit — we’re talking about selling members of the military an addictive and deadly product. It’s hard to see how that’s really a benefit, but that argument does get made.”
3. The NEJM Perspective article emphasizes that public health advocates need to support this initiative… Why? What are the implications for larger tobacco-cessation and cancer prevention efforts?
“Having a tobacco-free military sets a great example. It means that for young people who want to join the military, they’re much less likely to start smoking if they know they won’t be able to continue once they join. And once personnel leave the military, we won’t have that pool of people at a higher risk of smoking rejoining civilian life and increasing smoking rates in general. It would be a significant victory.”