The Road to Progress in Lung Cancer Treatment

A Conversation With Giuseppe Giaccone, MD, PhD

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Giuseppe Giaccone, MD, PhD

I think we should shift more of our research efforts to earlier-stage disease. Prevention is one area that needs much more attention, and screening plays a part there.

—Giuseppe Giaccone, MD, PhD

Despite promising new agents and therapeutic approaches, 5-year lung cancer survival rates have lagged far behind those of most other malignancies. To shed light on some of the important issues facing lung cancer experts, The ASCO Post recently spoke with internationally recognized lung cancer researcher Giuseppe Giaccone, MD, PhD, Associate Director for Clinical Research at the Lombardi Comprehensive Cancer Center, Georgetown University in Washington, DC.

Career Highlights

Please tell the readers a bit about your career before arriving at Georgetown.

I’m originally from Northern Italy. I did my medical training at the Turin Medical School. After that, I spent 2 years, from 1988 to 1990, in the Medical Oncology Branch of the National Cancer Institute (NCI) under the direction of John Minna, MD. I then moved to the Free University Medical Center in Amsterdam as a senior oncologist, and was appointed Head of Medical Oncology in 2003.

In 2007, I returned to the NCI as Chief of the Medical Oncology Branch. The NCI offered a tremendous opportunity for me to do basic research, but clinical research was a bit more challenging due to the amount of government regulation you have to deal with. I left the NCI at the end of 2012 to join the Lombardi Comprehensive Cancer Center at Georgetown University.

Current Role

What is your major function at the Lombardi Comprehensive Cancer Center?

I lead the Medical Thoracic Oncology Section, and my main job is to boost the research efforts at Georgetown University and the MedStar Georgetown Cancer Network, which includes two major hospitals in the DC area and a few other smaller hospitals in Maryland. My focus is largely on increasing the number of investigator-initiated studies in the institution and throughout the network.

My own research is centered on drug development and research on thoracic malignancies in the clinic. I also have a lab where we study mechanisms of resistance and tumor genetics in lung cancer and thymic malignancies. I have made a number of discoveries while at NCI, which we are advancing with our work here. We’re looking at novel genetic targets both in lung cancer and thymic tumors. There’s a lot of work to be done in this field, so I keep very busy.

European Cooperative Groups

You served as chair of European Organisation for Research and Treatment of Cancer (EORTC) Lung Cancer Cooperative Group from 1993 to 2000. Please shed light on that experience and how it contrasts with the Cooperative Group system in the United States.

The European cooperative group system is a lot less structured than the U.S. cooperative groups, in the sense that in Europe there’s really no central nationalized cancer institute. In fact, the EORTC is basically structured around volunteerism, which is driven by the individual interests of the participants. This creates a collegial environment that promotes rigorous scientific studies.

However, the culture has changed over the years since I chaired the Lung Cancer Cooperative Group. It’s expensive to run clinical studies on new drugs, and the economic challenges we face have made funding very competitive. More and more drug companies are running their own studies rather than partnering with cooperative groups, so that adds another challenge for the group system as a whole.

That said, although the U.S. groups face these same issues, the advantage in Europe is the socialized health-care system that funds some of the costs involved in research are being conducted in these groups. For instance, if you’re conducting a trial that requires a computed tomography (CT) scan every two cycles, and that is considered standard, the health-care system will pick up that cost. This not only makes it less expensive to run trials, it creates a more dynamic system than we have in the United States.

Accrual Issues

Poor accrual is a persistent problem in launching trials in the United States, with only 3% of our adult patients participating in trials. Does the socialized system of European countries have better results in trial accrual?

I believe it does. The socialized health system makes the accrual process less complicated simply because the coverage is universal, which makes the paperwork less onerous. Moreover, in Europe it is easier to accrue patients in studies that are placebo-controlled than it is in the United States. I think culturally there’s less reluctance by the public to participate in a trial in which they might receive a placebo instead of an active drug.

This is important because, for instance, studying the new molecularly targeted agents is different from studying traditional chemotherapy, and in placebo-controlled trials we can detect subtle tumor behavior. Of all the European nations, I think that the northern countries are the most open-minded about placebo-controlled trials.

Screening Challenges

Most agree that detecting early-stage lung cancers improves survival. However, whether to screen high-risk populations for lung cancer is still a matter of contentious debate. What’s your take on this issue?

This is a major debate, but ultimately I believe CT screening in high-risk individuals will be approved by Medicare and move forward. That said, it will present huge challenges because once you begin population screening you need to deal with the risks involved in overdetection of benign nodules.

Even specialized centers will be challenged by the harms to patients associated with inevitable overdiagnosis. Once approved, it will take years to ensure that all screening centers are equipped to meet standardized criteria.

Epidemiology Shift

Is there any significant change in lung cancer epidemiology that researchers and clinicians need to be aware of?

The most striking changes are in the populations now presenting with lung cancer. When I began working in this disease, it was almost always a tumor that presented in long-term smokers. But over the past decade we’ve seen a dramatic shift, whereby the majority of new cases present in nonsmokers and exsmokers. I’ve noticed an alarming number of nonsmokers and young people, especially young women who come into the center with a diagnosis of lung cancer.

We really don’t understand what’s driving this epidemiologic shift. We need to spend more time studying this phenomenon so we are prepared to treat these new groups of patients.

Future Directions

What direction should we take in this very difficult disease?

First, the drug industry puts tremendous emphasis on developing new drugs that treat advanced cancer. However, at least in lung cancer, this is probably no longer a viable strategy. We’ve tried it for decades now. I think we should shift more of our research efforts to earlier-stage disease. Prevention is one area that needs much more attention, and screening plays a part there.

We also need to move as fast as possible in developing agents that work in the adjuvant setting. There has been some work in this area, but unfortunately it takes many years for results. So we should try to develop some mechanisms by which we can test novel ideas in the adjuvant setting without having to wait years for the results.

Although targeted therapies have increased survival in patients with advanced disease, the increase has remained very small at best. The challenge remains to find something that will have a major impact for the whole population. But even with the new therapies, including the addition of immunotherapy, it doesn’t look like we’re going to be able to achieve cures in these patients. So moving these advances upfront to after or even before surgery, could be the way to progress in the future. ■

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