Killing Cancer: What Vincent DeVita Wants You to Know

OncologyLive, Vol. 17/No. 7, Volume 17, Issue 7
Partner | Cancer Centers | <b>Yale Cancer Center</b>

Vincent T. DeVita Jr, MD, discusses his insights into the operations of the FDA and the National Cancer Institute will hold a special appeal for oncology specialists and healthcare providers in his book, "The Death of Cancer."

Vincent T. DeVita Jr, MD

For the past 50 years, Vincent T. DeVita Jr, MD, has been one of the world’s leading oncologists and one of the field’s most innovative thinkers. He developed the first successful strategy to cure adult cancer with a combination chemotherapy regimen and led the National Cancer Institute (NCI) at a time when many vital treatment concepts were just being translated into clinical practice.

Now, DeVita has offered an insider’s view of those years in a recently published book, The Death of Cancer. The book, coauthored by his daughter, the science journalist Elizabeth DeVita-Raeburn, takes the reader on a compelling journey through DeVita’s struggles to advance cancer care, often in the face of colleagues hostile to new ideas and a political establishment that stymied progress.

Although the book is written for a lay audience, DeVita’s insights into the operations of the FDA and the National Cancer Institute will hold a special appeal for oncology specialists and healthcare providers. He forcefully argues for dramatic changes in the oncology drug evaluation and approval system that would give the nation’s cancer centers a more vital role and streamline the development of new therapies.

At age 81, DeVita remains on the faculty of Yale School of Medicine, where he is a professor of medicine, epidemiology, and public health. He is working with his co-editors on the 11th edition of Cancer: Principles & Practice of Oncology, the seminal and widely used textbook of cancer medicine. He still sees patients in consultation and he still teaches. “It’s part of the benefit of growing older,” DeVita said in an interview. “You have more time to sit back and look at the field and make judgments about it.”

OncLive: What prompted you to write The Death of Cancer?

DeVita did just that when he sat down with Maurie Markman, MD, editor-in-chief of OncologyLive, for an extensive interview in March.DeVita: The American people paid over $100 billion in taxes for the war on cancer. I was in an unusual position in the sense that I was in the right place at the right time. I was there at the National Cancer Institute before the Cancer Act was passed. The work I did was partly responsible for the philanthropist Mary Lasker getting interested in cancer. And then I wound up running the whole program, and I wound up at two major cancer centers. Then, I had the opportunity to be president of the American Cancer Society.

What is the major message you wanted to convey in the book?

As if I didn’t have enough experience, I got cancer myself. So I said to myself, a person in that position should really recount their experiences so that people know what they got for their money from somebody who saw it happening.That the war on cancer not only is winnable, but it’s actually being won. People don’t appreciate the significant change in the whole cancer field since the Cancer Act was passed back in 1971. The mandate of the war on cancer was to support research, and for the application of the results of research to reduce the incidence, morbidity, and mortality from cancer. In the Cancer Act itself there was never any mention of timespan. So since 1971 we have put 65% of the $100 billion into research. The incidence and mortality rates have been coming down since 1990-1991. It’s never easy to be treated with cancer but the morbidity is way less than it was.

The message is that we’re not only winning it, but it’s winnable. And I mean the latter because the new targeted therapies and the immunologic therapies are not even in these data. They’re just hitting the clinic, so the best is yet to come, and we know they’re going to be good.

Is there also a message for medical professionals—either oncologists or generalists?

I think we need an optimistic message to people. One of the reasons people are confused is that when we treat people with cancer, we want them to go home and live a perfectly normal life, and they do. The great majority of them don’t walk around and say, “I had cancer.” Some do, some become activists. But the great majority don’t. The ones you see generally are people who are suffering from it, and they’re much more visible. So people don’t appreciate how many people are being cured already of their cancer.As I point out in the book, there are some doctors who are not enthusiastic about treating patients with cancer. There’s always been this tug of war. You have cancer, it’s a self-fulfilling prophecy. It’s a lethal disease so you don’t treat it. If you don’t treat it, it’s a lethal disease. And some cancer patients get themselves in the hands of doctors who don’t believe [they can help].

You advocate talking about the concept of being cured with patients. What are your thoughts on that?

If you’re newly diagnosed with cancer and the doctor says, “you’ve got cancer, there’s nothing I can do for you,” you should find another doctor because there’s something you can do for virtually everybody nowadays with cancer.Nowadays I find that the fellows are not encouraged to use the word “cure.” So I’m a little bit of an outlier at Yale. [We say] we don’t know that you’re cured. It’s very conservative. It’s more like being a little afraid that if you encourage patients [to think] that they’re cured and they relapse, you take the blame for them relapsing.

I think patients would rather be free of cancer. They don’t want to be told that you’re not cured, we can’t be sure you’re cured. They want to go home and feel comfortable. So I think there’s a time almost with every cancer when you know that if they haven’t relapsed after treatment, they’re not likely to relapse.

For example, in Hodgkin disease it turns out to be about 4 years—if they go into remission and stay in remission, and are off treatment for 4 years. We’re doing the 45-year follow-up of our first group of 188 patients.1 Those patients are cured. They’re alive, free of disease, and lived a perfectly normal life. My feeling is you should say to them, “you’re cured,” and give them the optimism.

Now we have very interesting things happening in the cancer field. The best example I know of is chronic myelocytic leukemia. This is a disease that, when I started out, was uniformly fatal. Now patients take a pill and they live a perfectly normal life. And when they develop resistance to the pill, the pharmaceutical industry has developed four others that they could take, and probably we will keep doing that. So they aren’t cured, they’re just living a perfectly normal life.

In the book, you’re quite open and eloquent in your description not only of your own experience with prostate cancer, but also about the experience of your son who was diagnosed at age 9 with a rare illness. How have those experiences influenced you?

So we have a different category of patients who are able to live with their cancer for a normal life as opposed to those who have no evidence of cancer. And I think we’ll see more of that. Using some of the immunotherapy approaches, we’re seeing patients whose cancer just goes into abeyance but they still have evidence of disease if you look hard enough. It’s a new category so you need to explain that difference to patients. But when it’s possible to say with some confidence they’re cured, I like to say, “You know, you’re very likely cured of your disease.”My son had aplastic anemia. He was put into a laminar airflow room to protect him from getting infections. And he stayed there for about 8 years. Except for some excursions out in what we called the spacesuit—we worked with NASA and let him walk out with a spacesuit—he never left that room.

I thought I had a lot of empathy for parents of children who died of leukemia or had leukemia, but it’s a whole different experience to go through it myself. I think it made me a better doctor. It changed me in a whole host of other ways.

When I developed prostate cancer, I think I did what a lot of doctors do—tend to ignore it and do what I say, not what I do. When I finally was diagnosed, it was a difficult case. The prostate was very large. I realized that what I normally did for patients to navigate for them and find places for them to go to get the best therapy, I couldn’t do for myself.

You discuss a number of controversies throughout your career, starting with the resistance you encountered to the concept of combination chemotherapy. Why do you think there was so much reluctance to consider these innovative approaches, which now are standard of care, and do you think we still see reluctance toward novel strategies?

So I had to ask my colleague Steve Rosenberg [of the National Cancer Institute] to do that for me. He did a great job and steered me to one of the finest surgeons in the country, Peter Scardino [of Memorial Sloan Kettering Cancer Center]. So it gave me an insight into being in the medical system, how difficult I knew it was. But then when you experience it first-hand it’s a little bit different. It changed me quite a bit.In the 1960s, the thought that you could cure cancer with drugs was considered insane, and the doctors who were doing it were in fact called insane. Using drugs in combination was considered bad medicine, and that primarily stemmed from using antibiotics in combination. Epithets that were thrown around at Grand Rounds at people who were trying to do this were extraordinary.

We did [use combination chemotherapy] at the National Cancer Institute, which was a somewhat protected environment where we could actually do these things and take some criticism, but nothing stopped you from doing it. You were sort of limited by what was between your ears. It would have been impossible to do it elsewhere.

Today, I do see the same thing. I see people who still are reluctant to do innovative things. For example, we have proof of principle that we need combinations of different agents to cure cancer. With very few exceptions, you need combinations.

In fact, you’re looking at it now in melanoma with immunotherapy where clearly immunotherapy that is combined is better than a single immunologic agent.

What do you think can be done to change the way the FDA operates?

I don’t know why we have to keep proving this all over again. But we’re proving it all over again because the FDA requires us to prove it all over again. I think the FDA is still in the last century and needs to come into this century. I think one of the problems we have is we’re overregulated. Doctors are fearful that if they do something a little off the beaten path, then they will be penalized for it and lose their ability to do research or be considered not collegial.One thing I tried to do is write the book. I thought it’s possible we could get the attention of the only people who could really fix this, which would be Congress.

I think what happens today is that doctors don’t realize where they are. They’ve been backed into a situation where the FDA essentially is practicing medicine and directing research. We do a handbook on chemotherapy, and if you look at a given drug, it will tell you, “this drug has been approved for use after they’ve had this drug, before they’ve had that drug, after they’ve had this drug, and at this stage,” and so forth.

This is somebody 3000 miles away from the patient telling you exactly when you can use it. Most of the innovative work that’s going on is usually done in the aftermarketing period. And so the FDA essentially has paralyzed the aftermarketing period by doing this.

I think there is a simple solution, and I talk about it in the book. I think that the FDA and the National Cancer Institute should delegate all phase I and II clinical trials completely to the cancer centers. That is, the FDA and the NCI could reserve the right to come in and do audits. They have it now, they could do it then.

But they should delegate all the responsibility. So you can start a phase I trial in your cancer center and if you want to make changes you don’t have to go back to the NCI or the FDA, you can make changes with your own internal review committees, and you can do that for phase II studies where most of the good stuff is happening. I also think that the FDA should change how it approves drugs. It should approve drugs based on their safety, but safety in the context of the patient who is going to be using it. Safety is a different creature when you’re using it for an antihypertensive drug that a patient is going to take for the rest of their lives, versus a cancer patient where it’s cure or not cure in a very short period of time. But safety is important. Safety and the ability to hit a target, a biologic target.

So if you develop a drug, a receptor you know is important, and it hits that receptor, they should approve it. You put it into the therapeutic armamentarium for the doctors, and the doctors are able to mix and match the way they want to use the drugs.

I describe a meeting that in the early days we called the Society of Jabbering Idiots [at the NCI]. It was the best meeting I’ve ever been to in my career because it was essentially a war room where all the data that was going on in the wards was matched with the data in the labs, and we could make adjustments to the protocol and go right on the ward and do it. Nowadays it can 800 days to take those adjustments back through the review system.

You delegate the responsibility for this to the cancer centers, they could each have their own society of jabbering idiots—with the excitement, knowing the biologic pathways and all the mutations— and be able to mix and match therapies.

What’s intriguing about this is that it would not only make things a lot easier, it would cost less. You don’t need an infusion for the moon shot to change this, you just need the FDA and the National Cancer Institute to give up some power and authority. Unfortunately, in Washington no institution gives up power and authority voluntarily.

So they’re going to have to be squeezed to do it. The cancer centers were developed to do this [research]. Although I criticize them in the book because they had growing pains, a lot of them are at the point where they could do this now and do this easily, and they have many more experts to do this than the FDA will ever have in their entire life. So that and the whole Compassionate Use Program [through which patients have access to investigational drugs] need to be taken from the FDA and put back where they were in the 1970s.

Looking forward, where do you think cancer treatment is heading? Is it immunotherapy? Is it targeted therapy? Is it combinations?

In the book, I go over the eight hallmarks of cancer that Weinberg and Hanahan wrote about in a landmark paper2 and point out that basically, when we’re successful, we’re attacking two or three of the hallmarks. In the future, we’re going to have to be thinking about attacking all of the hallmarks. Immunotherapy, or the failure of immunosurveillance, is one of them. It was in 1996, I believe, when the discovery of the checkpoint inhibitors changed our whole thinking. We struggled for years trying to figure out why we couldn’t boost the immune system to eradicate cancer. I don’t think immunotherapy by itself will be the answer to cancer. I think it’ll be coupled with chemotherapy and other forms of treatment, if we have the freedom to put that together—antihallmark therapy as I say in the book.

Can we fix that?

What would you consider to be some of the major breakthroughs over your many years in the oncology field?

But good luck in the current regulatory environment. The FDA forces drug companies to test their drugs one at a time. And what you need to do is test things in combination.Yes, I think if you delegated the phase I and phase II clinical trials to cancer centers, you could do it any way you wanted to. All we have to do is assure the safety of patients and have the effective oversight; we all have our health, our human investigation committees. It’s fixable, and it’s fixable pretty quickly and at less cost than the current cost. Here we have an idea that actually would work and cost less money and would advance the cause of cancer treatment prevention and diagnosis by a great deal.There are almost too many to mention. But if you think of cancer treatment, there have been three paradigm shifts that I think have made a major impact. The first was the ability to cure advanced cancer with combination chemotherapy. That opened up the whole field of adjuvant treatment for breast cancer and colorectal cancer.

The second was when Brian Druker put targeted therapy on the map in chronic myelocytic leukemia with a drug that hit the BCR-ABL mutation.3 We’re now using that approach in lung cancer, in melanoma, and many cancers as we sequence the genome and find the targets.

You were chosen by fellow oncology specialists as part of the inaugural class of Giants of Cancer Care award winners in 2013. What is your feeling about being included in this honor?

The third was the discovery of the checkpoints in immunotherapy. I think those are the three paradigm shifts that occurred in cancer treatment in my lifetime that are all having a significant impact on the ability to treat cancer.It’s a great accolade. It’s nice to be recognized by your peers, and the company was pretty heady company. All the people I’ve admired over the years were in that group and continue to be added to the group. I think it’s a great honor and I think people look forward to being considered a Giant of Cancer Care.

References

  1. Canellos GP, Rosenberg SA, Friedberg JW, Lister TA, DeVita VT. Treatment of Hodgkin lymphoma: a 50-year perspective. J Clin Oncol. 2014;32(3):163-169.
  2. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646-674.
  3. Talpaz M, Silvee RT, Druker BJ, et al. Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. Blood. 2002;99(6):1928-1937.