A Conversation with Craig B. Thompson, MD

The President of Memorial Sloan-Kettering Cancer Center shares his thoughts on the future of cancer care.

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2.17.53_thompson.jpgIn November 2010, Craig B. Thompson, MD, was named President and CEO of Memorial Sloan-Kettering Cancer Center (MSK) in New York, succeeding Harold Varmus, MD, who is now Director of the NCI. A cancer clinician and researcher, before coming to Memorial Sloan-Kettering Dr. Thompson was Director of the Abramson Cancer Center at the University of Pennsylvania and Associate Vice President for Cancer Services of the University of Pennsylvania Health System.

As the 1-year anniversary of Dr. Thompson’s tenure approached, he talked with The ASCO Post about recent discoveries in more effective therapies for such deadly cancers as metastatic melanoma and the challenges that remain in advancing better targeted treatment for other currently incurable and difficult-to-treat cancers.

Ambitions and Challenges

You’ve been President of Memorial Sloan-Kettering Cancer Center for a year. Would you share some of your reflections on that experience?

Joining MSK has been a transformative experience for me, both as a medical oncologist and as a cancer researcher. For a very long time I’ve been involved in trying to develop quality cancer care at matrix cancer centers embedded within tertiary care facilities. However, this is my first experience in a fully dedicated cancer hospital, and it has been an amazing experience.

What are some of the challenges you face?

Institutions like MSK and other dedicated freestanding cancer centers have really captured the world’s attention by showing that cancer is a treatable disease and that we can push further and further into earlier, preemptive diagnoses.

The challenge going forward for freestanding disease-specific hospitals is to figure out how to survive, given the needed changes in American health care. Over the past 40 years, cancer treatment has improved to the point that, today, two-thirds of American patients with cancer are doing well 5 years after their diagnosis. And because their disease is either cured or largely controlled, they can get back to their normal lives.

Our mission now is to focus our attention on the one-third of patients with cancer who don’t do as well. These are patients with rare cancers and cancers that have proven hard to treat like pancreatic, liver, kidney, and lung cancer, all of which are still difficult to diagnose early and for which treatment options are limited.

How do we most effectively continue to do research that deepens our understanding of this disease, and how do we deliver new therapies that can help these patients? That’s where the staff and I have redoubled our efforts at MSK.

Therapeutic Advances

How would you describe the state of the art in medical oncology?

There are now three different treatment modalities—immunotherapy, oncogene-targeted inhibitory therapy, and chemotherapy exploiting the unique cellular dependencies created by oncogenic transformation—that are starting to deliver on the promise that came with the decoding of the human genome, our increased understanding of the basic biology of cancer, and how cancer interacts with the rest of the body.

For the first time, we are seeing immunotherapy make good on its potential. We have sipuleucel-T (Provenge), in which a vaccine approach has shown a survival benefit in prostate cancer. And we see how blocking immune system inhibitors with drugs like ipilimumab (Yervoy) allow the immune system to mount a sustained attack on cancer cells. The idea that we can harness the power of our own bodies to fight cancer represents a tremendous opportunity for cancer biologists. And it fits in with the other two advances that have also shown tremendous advantage this past year.

2.17.53_quote.jpgOne is the development of targeted therapeutics beyond imatinib (Gleevec). For the first time, we see BRAF inhibitors such as vemurafenib (Zelboraf) successfully targeting RAF-based melanomas. We’ve also seen how ALK inhibitors can target oncogenic ALK rearrangements. Then there are therapies that exploit the unique properties of certain cancer cells—like the proteasome inhibitor bortezomib (Velcade)—that have proven effective in multiple myeloma.

So the question for us becomes, how do you use these therapies in combination? One of the things we think a dedicated cancer center should do is to mix and match these approaches in an effort to achieve the best possible outcomes.

For example, in melanoma we have the advances with vemurafenib, pioneered here by Paul Chapman, MD, and the work on ipilimumab, by James Allison, PhD, Chair of the Sloan-Kettering Institute’s Immunology Program. Both of these agents have shown exciting therapeutic potential.

What’s interesting about the RAF inhibitors like vemurafenib is that nearly every patient with a RAF mutation experiences a benefit, but it only lasts 6 months to a year. In contrast, ipilimumab only helps a fraction of patients—between 25% and 35%—but some of those patients experience long-term disease-free survival. So what’s making the difference? And how does one combine those two therapies so they are not antagonistic but are actually synergistic? These are the kinds of questions we are asking—and answering—at Memorial Sloan-Kettering.

Collaborative Research

Recently, researchers at MSK conducted a phase I trial of a novel T-cell–based gene therapy approach to treating chronic lymphocytic leukemia and B-cell acute lymphoblastic leukemia. A similar study was conducted at the University of Pennsylvania. Both studies showed promising results, and now researchers from the two institutions are launching a phase II study. Can you talk about the importance of this kind of collaborative work?

We have a grant from the NCI Special Translational Research Acceleration Project (STRAP) Program to demonstrate that two centers can work collaboratively and use the same protocols to launch a clinical trial. We’re developing the protocols here under lead investigator Renier Brentjens, MD, PhD, and working with Carl H. June, MD, Professor of Pathology and Laboratory Medicine at the University of Pennsylvania. I think we’re going to see more of these sorts of collaborations among cancer centers, because they can result in validating the reproducibility of new experimental approaches.

How we integrate this new approach into state-of-the-art patient care is going to be extremely important. Similarly, how we incorporate advances in surgery, radiotherapy, and medical oncology and then disseminate that information to other hospitals will be critical. That’s our job: to develop these advances, with the ultimate goal of making them standard practice, so they can be adopted by other hospitals and clinicians.

Future of Oncology

ASCO and other organizations have identified an impending shortage of oncologists. What advice would you offer to the next generation of clinicians and researchers to encourage the pursuit of a career in oncology?

I think this is a really exciting time in oncology for all the reasons that we’ve discussed. When you consider my generation of oncologists, whether we chose to practice surgery, radiotherapy, or medical oncology—we all came to our careers knowing that for the vast majority of cancers there weren’t a lot of effective therapies we could offer patients. We were giving nonspecific chemotherapeutic agents, performing big surgical procedures, and using nonmodulated radiation therapy, so the side effects were enormously debilitating to patients.

2.17.54_quote.jpgToday, we understand much more about the molecular underpinnings of cancer and how surgery, radiotherapy, and medical oncology can be used in concert to increase treatment effectiveness and decrease side effects. The number of new chemotherapies that allow patients to live full, active lives with their cancer—dealing with it as a chronic disease—is unparalleled.

All these advances offer tremendous hope for patients, and they present tremendous opportunities for greater job satisfaction for physicians, who now have the chance to be part of the revolution that changes cancer from a death sentence into a manageable disease.

Cost of Care

With the cost of cancer care so high and skyrocketing national deficits, can we afford to deliver the best possible cancer care for all Americans?

Analyzing what is affordable at this particular time in history is difficult. People wondered whether we could afford to build the tuberculosis sanitoriums that were set up around the country in the early 1900s. Then researchers discovered the antibiotics that eradicated TB—both as an individual disease and as a public health problem—and suddenly treating TB became very inexpensive.

We are seeing the same sort of revolution in cardiovascular care. As the most effective cholesterol-lowering statins come off patents, the cost of these drugs is decreasing dramatically. With better control over heart disease, people with these once-terminal illnesses are living longer, healthier, and more productive lives, caring for their families, getting back into the workforce, and contributing to their communities. That’s really the goal, but it’s going to take economists to analyze whether the tradeoff is worth it.

New therapies to fight disease are always going to cost more money. As opposed to our cardiology colleagues, who have a number of strategies to control heart disease, we’re still at the halfway point in cancer. We can treat some cancers effectively, but there are others that we still don’t understand well enough to know the best ways to diagnose them early or to optimize care so that patients can fulfill their life goals.

We are not at the endgame. We need to continue to further our understanding of cancer so we can eliminate the problems of treatment toxicities and the damage that can still occur as a result of surgery and radiation therapy, even with modern techniques. In the final analysis, we need to make treatment of all kinds simpler and more effective. This will not only make things better for patients, but will also bring down the cost of care. ■

Disclosure: Dr. Thompson reported no potential conflicts of interest.