Print BCTV: VEGF Visionary -- ASCO State of Cancer Care; Profiles inInnovation: VEGF discoveries

VEGF Visionary

Transcript of BioCentury This Week TV Episode 183



Dr. Richard Schilsky, Chief Medical Officer, American Society of Clinical Oncology

Michael Elman, MD, Elman Retina Group

Dr. Napoleone Ferrara, Distinguished Professor, University of California San Diego School of Medicine





Affordable Care Act


Choosing Wisely

Quality Oncology Practice Initiative

Vascular Endothelial Growth Factor (VEGF)

Genentech, Inc.

Avastin, bevacizumab, Genentech, Inc.

Lucentis, ranibizumab, Genentech, Inc.

Food & Drug Administration

Factor X

Eylea, aflibercept, Regeneron Pharmaceuticals, Inc.

Lasker Awards



Steve Usdin, Senior Editor




STEVE USDIN: Cancer treatments are improving, but can healthcare keep up? The American Society of Clinical Oncology is warning about racial disparities, a looming shortage of specialists, and unsustainable costs. We'll hear from ASCO's chief medical officer, Dr. Richard Schilsky. And in Profiles in Innovation, we'll learn how a search for a cancer cure led to an incredibly effective treatment for blindness.


I'm Steve Usdin. Welcome to BioCentury This Week.


NARRATOR: Connecting patients, scientists, innovators, and policymakers to the future of medicine -- BioCentury This Week.


STEVE USDIN: The American Society of Clinical Oncology's first State of Cancer Care report has some good news. There are nearly 14 million cancer care survivors in America. And the number is increasing. ASCO also makes some troubling predictions.


Cancer will be the leading cause of death in America by 2030. And there will be a serious shortage of oncologists by 2025. One factor -- the economics of medicine is driving small community-based oncology practices out of business. Already, there's a shortage of oncologists in rural areas.


Average survival statistics hide disturbing facts, including huge racial disparities in outcomes. Finally, ASCO warns of unsustainable cancer care costs, driven by expensive, unnecessary treatments and high drug costs. I'm pleased to be joined by Dr. Richard Schilsky, chief medical officer of the American Society of Clinical Oncology, ASCO. Dr. Schilsky, the report that ASCO has put out has got some good news -- increasing survival rates for cancer patients.


But it also has some troubling news. It suggests that cancer will be the leading cause of death in America by 2030. What's driving those numbers?


RICHARD SCHILSKY: Well, the statistic is that by 2030, cancer will be the leading cause of death in America. It's being driven largely by the aging of the population, the fact that the baby boomers are now all entering or well into their '60s. Cancer is largely a disease of older people.


And so there's a much larger segment of the population at risk of getting cancer. There may also be some contribution from lifestyle practices, in particular, obesity. We're learning that there's a substantial link between obesity and risk for a number of different kinds of cancer. And since we know we have an obesity problem in this country that may be a contributing factor as well.


STEVE USDIN: One of the other things that may be one of the more troubling things also about in the report is data about racial disparities and outcomes in cancer. So the overall numbers showing increase in survival, underneath that, there's this enormous racial disparity. How big are the disparities, and what are causing them?


RICHARD SCHILSKY: Well, they're substantial. We know that a person diagnosed with cancer today has a substantially better chance of surviving five years than they did 20 or 30 years ago. So now, someone's new cancer diagnosis, that person has nearly a 70% chance of five-year survival, compared to roughly 50% 30 years ago. But the benefits of all these improvements in cancer screening, prevention, and treatment are not being achieved by all segments of the population, particularly African Americans, where their outcomes are not as good.


The reasons for that are not entirely clear. Some of it is access to care, which is driven, of course, by socioeconomic issues. Some of it is cultural beliefs in different communities that limit their willingness to consider certain kinds of therapies.


There may be some component of biology, although generally speaking, when we can determine that people in different racial groups get equivalent therapies, they get equivalent outcomes. So biology may be only a small part of what's going on. And it may really be mostly access to care.


STEVE USDIN: And access to care, one of the other things that the report talks about is the Affordable Care Act. And it says that the Affordable Care Act by itself isn't likely to end these kinds of disparities. One of the reasons it cites is that a lot of the expansion in coverage is due to Medicaid. And it says basically that Medicaid coverage for cancer patients isn't as effective as other forms of insurance coverage.


RICHARD SCHILSKY: So historically, that's been the case. We know that patients with cancer who have exclusively Medicaid insurance generally have outcomes similar to people who have not had any insurance whatsoever. What we hope will change now going forward is that as more and more people become eligible to receive insurance, even if it's Medicaid, that will get them into the healthcare system sooner.


It will get them access to screening strategies, prevention strategies, early-diagnosis strategies. So the hope is that going forward, they'll have a better chance of having a cancer diagnosis sooner rather than what is almost for sure the case in the past, where the Medicaid population has not had good access to care and has had cancer diagnosed at a far later stage.


STEVE USDIN: The United States has 3.8 oncologists per 100,000 people, but they aren't distributed evenly. Here's a snapshot. More with Dr. Richard Schilsky in just a moment.





STEVE USDIN: We're talking with ASCO's chief medical officer, Dr. Richard Schilsky. Dr. Schilsky we just saw this map that showed the uneven distribution of oncologists across the United States. What effect does that have on patients?


RICHARD SCHILSKY: The big problem, of course, is that there are sections of this country that have no oncologists available. It's estimated that roughly 70% of the counties in the United States have no oncologists working in those areas. Most of the oncologists -- there are roughly 13,000 oncologists practicing in the United States. Most of them are concentrated in the Northeast, on the West Coast, around the Great Lakes.


So the central part of the country and the South is where the risk is, if you will. What it means essentially is that cancer patients have to travel longer distances to find an oncologist. And of course, that's a difficult thing.


Cancer patients are often weak, debilitated, they need family members to take time away from work to help them get to their cancer appointments. So when you have this uneven distribution, it creates even greater stress for the patients who don't have good access.


STEVE USDIN: And there's data in the report also that suggests that things might get worse, because you talk about two trends -- one, a looming gap in the number of oncologists that are available, and also big demographic changes in the oncology workforce.


RICHARD SCHILSKY: Yeah, you're exactly right. So there's two critical things that are happening. First of all, a significant fraction of the oncologists in the country, roughly 20%, are already approaching retirement and are likely to retire in the next 10 years. The rate of replacing those oncologists is not keeping up with the likely demand for oncology services.


So there's going to be a widening gap between the need for oncologists and the number of oncologists who are actually practicing. When you add to that the fact that the oncologists are not evenly distributed around the country and that oncologists who are in small practices -- one or two physicians -- have been facing considerable financial stress in recent years, and many of them are actually closing their practices, reducing their hours, or consolidating into hospital-based practices, there will be parts of the country where it'll be very difficult to find an oncologist.


STEVE USDIN: So is technology able to help out here in any way?


RICHARD SCHILSKY: Absolutely. And I think technology is one of the things we're going to be relying on a lot going forward, because technology is fundamentally about information exchange. So to the extent that we can connect doctors with other doctors, who can offer expertise and share experience, to the extent that we can connect patients to their medical care teams, 24/7, through a variety of technologies, and even connect patients to each other through various social networking services, we will be able to get people better connected to information, better connected to feedback, better connected to guidance, and help them deal with their illness and avoid unnecessary emergency room visits, unnecessary hospitalizations, of course which are also key drivers of the cost of care.


STEVE USDIN: So one of the other ways that technology might be able to help is the creation of so-called learning healthcare systems. That's something that ASCO has worked on. Briefly, what are you working on, and how real is it?


RICHARD SCHILSKY: So we're working on a health informatics system that we call CancerLinQ. CancerLinQ essentially is a giant IT project that will allow every doctor to learn from the experience of every patient in the system. It's a system whereby patients will contribute their electronic health records into a large data warehouse. And then that information, once de-identified, will be able to be queried for all sorts of information about the patient characteristics, the patient treatments, the patient outcomes.


Doctors will be able to go into the system, enter the characteristics of a patient, like the patients they're caring for, learn about the experiences, the treatments, the outcomes of other similar patients in the system. And we think by creating this huge database of clinical experience, it will give us the opportunity to learn from every single cancer patient, instead of just learning from the 3% to 5% of patients who participate in clinical trials.


STEVE USDIN: Thanks. Another thing I want to talk about is ASCO's concern about cancer costs. We're going to talk about that in just a moment. But first, a look at the escalation in cancer drug costs.




STEVE USDIN: We're back with ASCO's chief medical officer Dr. Richard Schilsky, discussing the cost of cancer care. Dr. Schilsky, the report highlights the increasing cost of cancer care and suggests that it's unsustainable. What are the problems, and what are some of the solutions that you see?


RICHARD SCHILSKY: So the costs have been going up dramatically in recent years. They're driven really by by two things -- the cost of drugs, which is skyrocketing, and the cost of medical services, which are very complex for cancer patients who have many acute complications during the course of treatment. On the services side, which is where the doctors really have some control, we are looking at various strategies to keep people out of the emergency room, keep people out of the hospital unless absolutely necessary.


Those two key drivers of cost. We've been participating in the last two years in a national campaign called the Choosing Wisely campaign, where we have listed in each of the last two years, five key things that doctors do that are not strongly evidence-based and are costly and we believe could be eliminated, like for example, giving people chemotherapy within the last few weeks of life.


So doctors need to do a better job. We need to think carefully about what tests we're ordering and why we're ordering them and how we're going to use the results and things of that sort. We need to communicate better with our patients, we need to give them access to our our medical staff to help guide them through their illness so that they don't just run off to the emergency room every time a problem develops.


But where we don't have much control is the cost of drugs.


STEVE USDIN: And the report highlights the costs of drugs. And I guess what it really brings up the question is, are they really worth it?


RICHARD SCHILSKY: Well, that's a difficult value judgment to make. Cancer patients, in many cases, are facing a life-threatening illness. Any improvement in survival could be viewed as important and beneficial to an individual. The problem is that many of the drugs that we're coming out with today, even the most effective ones, are effective in shrinking the cancer in a high percentage of patients, but the cancer tends to rapidly regrow.


So the ultimate impact on a patient's survival is relatively small. The cost of care has gone from roughly $1,000 a month 10 years or so ago to now more like $10,000 a month. And for patients who have a 20% or 30% co-pay, that's a substantial out of pocket expense.


STEVE USDIN: ASCO has got a project that you're working on to try to look at and assess the value of cancer drugs. Can you tell a little bit about that?


RICHARD SCHILSKY: So we're interested in actually shifting the conversation from just talking about the cost to really talking about the value. And in our view, value has at least three components to it. What is the incremental benefit of a new treatment in terms of survival? What is the incremental toxicity of a new treatment, if any? And what is the incremental cost of a new treatment?


And we're trying to put together an algorithm based upon those three dimensions of value to come up with, essentially, a rating system to say, this is a high value therapy, this is a less high value therapy. It means, of course, that a high cost therapy could also be high value. So if you have a high cost therapy that cures people with advanced cancer that might be viewed as a high value therapy.


But if you have a high cost therapy that produces only a small incremental benefit or is considerably more toxic, even if it produces a modest improvement in survival, that may be considered to be a lower value therapy. But we think that that the appropriate context is to talk about the value of care and less about the cost of care.


STEVE USDIN: That's really interesting. Very briefly, when is that going to be ready for prime time? When are we going to see it?


RICHARD SCHILSKY: So we we've been working on it for six months or so. We're beginning to roll it out internally to get some feedback from some of our members. And I suspect that by later this year, we'll be ready to go out publicly with this new algorithm.


STEVE USDIN: Dr. Schilsky, one of the things that the report also brings up is the need for better measurements of quality. Why is that needed? And what is ASCO doing about it?


RICHARD SCHILSKY: Of course, as physicians, our fundamental goal is to deliver the highest quality care to every patient. And we've been concerned for some time, particularly as we enter into a more and more cost constrained environment that if you try to ratchet down on cost, it could be at the expense of quality. And that's something that we couldn't tolerate.


So in order to assess that, we first have to figure out how to measure quality, and then to figure out how to improve quality. ASCO has had a program in place now for more than a decade called the Quality Oncology Practice Initiative, or QOPI. And QOPI is essentially a self-assessment project for oncologists, whereby they extract information from their patient's charts that measures their performance against established quality measures and guidelines.


We feed back to them information on how they're doing in certain key parameters of clinical practice. We show them where there are gaps and deficiencies. And then we help them to improve in those areas.


STEVE USDIN: Isn't there a need for some kind of transparency on that so that payers and especially patients would have some way of assessing the quality of care that particular providers and particular institutions provide?


RICHARD SCHILSKY: Absolutely. And in fact, as part of the QOPI program we introduced several years ago, a QOPI certification program. So there are now about 200 oncology practices in the country that are QOPI-certified.


They are free to advertise that however they wish in their communities. And we think of them as some of the best practices in the country, because they meet all of our quality standards.


STEVE USDIN: So one of the other things I guess that flows from quality is also payment reform. And that's another thing that's touched on the report. Very briefly, what do you think needs to happen to change the way that oncology services are paid for in the United States?


RICHARD SCHILSKY: So what we're advocating for is to stop paying doctors for what they do, but pay them for the results they achieve. And one of the things that we hope will happen will be repeal of SGR, which has been a very flawed reimbursement system for doctors, and to replace that with a system that will actually pay doctors to achieve better outcomes for patients and pay them for the cognitive work that they do, which is very prominent in oncology and pay them for all of the services they provide.


STEVE USDIN: Next, on Profiles in Innovation, how basic research on cows led to a cancer drug and a breakthrough treatment for a common form of blindness.


NARRATOR: Now in its 22nd year, visit for the most in-depth biotech news and analysis.




STEVE USDIN: The journey from basic scientific discovery to the creation of a new drug is long and arduous. It's rare for a single scientist to make a fundamental discovery and then go on to lead the development of a new drug.


Napoleone Ferrara navigated this path twice, bringing the world an important cancer treatment, and a therapy that's helping millions of people around the world avoid debilitating vision loss. Today, Dr. Ferrara describes his journey.


Wet age related macular degeneration-- AMD-- a leading cause of vision loss, usually afflicts people after age 50. It often starts as blurred central vision. Shapes are distorted. The blurry spots get larger, sometimes turning into black spots.


Diabetes patients are at risk of macular edema, a similar disease that causes severe loss of vision. AMD is devastating, according to Dr. Michael Elman, a retinal specialist who's participated in many clinical trials.


MICHAEL ELMAN: Ultimately, you can become legally blind or worse, where you have this big, black area in the center of vision. So you can see around it, you can see that there's a person in front of you. But even if you've known that person for 50, 60 years, until that person opens his or her mouth, you won't know who it is. You'll know that that's maybe a man or a woman, but you won't be able to identify the person.


STEVE USDIN: 200,000 people in North America are diagnosed with wet, or neo-vascular macular degeneration every year, and about 750,000 have diabetic macular edema. Many will be able to avoid blindness because of a scientific journey that started in a university lab, moved to a biotech company, and led to approval of a cancer drug.


In the early 1980s, while he was a post-doctoral researcher at the University of California, San Francisco, Napoleone Ferrara found a substance in the pituitary gland of cows.


This substance made cells that line blood vessels grow. These cells are involved in the formation of new blood vessels -- a process called angiogenesis. After joining Genentech in 1988, Ferrara isolated a protein from the cells he'd found in pituitaries. He called it Vascular Endothelial Growth Factor -- VEGF.


His team created a monoclonal antibody that blocks the effects of VEGF. The hope was, this would lead to a drug to prevent angiogenesis in cancer tumors. Based on experiences with other angiogenesis inhibitors, expectations for VEGF were modest. But the first animal tests conducted in 1992 were surprising.


NAPOLEONE FERRARA: We implanted tumor cells in mice, and then we treat the mice with anti-VEGF antibody. At that time, to our, I must say, astonishment, we found that, you know, blocking of VEGF alone could have, in some cases, a very dramatic inhibitory effect on tumor growth.


I would say astonishing because, once again, it is -- no one has done this -- has shown it, you know, blocking a specific angiogenic factor, and it inhibits tumor growth.


It was believed in those days that, you know, to have a significant effect to inhibit many factor -- maybe 10 or 15 different factors. So the fact that blocking one factor could have such effect was certainly unexpected.


STEVE USDIN: Ferrara's original anti-VEGF antibody was created using mice. Genentech created a human version that it called Avastin.


NAPOLEONE FERRARA: This humanised antibody, which ended up being known as Avastin, or bevacizumab, started a clinical trial in cancer in 1997. It was actually -- it was finally approved by the FDA in 2004 for colon cancer.


STEVE USDIN: But Ferrara wasn't finished. As early as 1948, scientists postulated that an unidentified angiogenic substance, dubbed Factor X, caused by diseases like AMD. In 1994, Ferrara started investigating VEGF's potential role. He learned it might be the long sought Factor X, and that a drug like Avastin might treat eye diseases.


Ferrara decided that infusing an anti-angiogenesis factor into the blood of elderly patients could cause unacceptable side effects. Instead, Genentech tried intro vitriol injections, injecting the antibody directly into the eye.


NAPOLEONE FERRARA: We initially thought of giving a systemic Avastin, just like the way it's given to cancer patients. But then it became clear that this could result in some cardiovascular side effect like hypertension and sometimes even more serious effect, which especially in an elderly populations, like, you know, AMD patient, it could be very danger.


STEVE USDIN: Genentech decided to make a new antibody that was likely to be safer and more effective in the eye than Avastin. They called the product Lucentis. The results were incredible.


In one of its phase three trials, 95% of Lucentis' patients maintained vision at year one, compared to 62% who received a sham, or placebo, treatment. At a time when the best treatments only delayed an inevitable decline to blindness, Lucentis exceeded reasonable expectations. Many patients experienced sustained improved vision for years.


MICHAEL ELMAN: It's revolutionized what I do for patients. Before, we had very little of what we could do. We had very little available to help them. We had laser. If they were really advanced with scar tissue, we could do surgery in diabetics.


Today, we're able to intervene a lot earlier. With these medications, it's turned it from a surgical disease into a medical disease -- into one that we treat with medications.


STEVE USDIN: Clinical trial results were so impressive that some retinal specialists didn't wait for Lucentis to be approved. In 2005, a Florida ophthalmologist reported success treating AMD with intra vitriol injections of Avastin. Within six months, Avastin was being widely used, with results similar to Lucentis.


Although Genentech raised safety concerns, many physicians continued to use Avastin after Lucentis was approved in 2006 because it was much less expensive. An NIH-sponsored trial called CATT concluded Lucentis and Avastin are equivalent for wet AMD.


The hunt for VEGF agents didn't stop. In 2011, FDA approved another anti-VEGF antibody, Eylea, from Regeneron Pharmaceuticals.


MICHAEL ELMAN: I treat patients with all three drugs. I tell them that there are drugs that are available from the FDA that are approved. In general, if patients have adequate coverage, I prefer to use a drug that is proven and labeled to do so.


If someone doesn't have any insurance, one would tend to use Avastin, because then you would either use that drug, or have nothing available.


STEVE USDIN: Ferrara's is discovery of VEGF and its role in the body was a scientific breakthrough. He didn't stop there. He turned the discovery into an antibody that fights cancer, and then into a drug that's restored sight and hope to millions around the world. In 2010, he was honored with the Lasker prize -- the most prestigious award in American science.


You can watch an extended interview with Dr. Ferrara online at That's this week's show. Remember to share your thoughts about today's show on Twitter. Join the conversation by using the hashtag #biocenturytv. I'm Steve Usdin. Thanks for watching.