Marking Bunn's Lifetime of Leadership in Lung Cancer Care

Paul A. Bunn Jr, MD

When Paul A. Bunn Jr, MD, arrived at the University of Colorado School of Medicine in 1984, there was no National Cancer Institute (NCI)-designated cancer center in the region. The Division of Medical Oncology had only four medical oncologists associated with the facility and a handful of patients participating in clinical trials. Today, the center boasts 55 faculty members in its Division of Medical Oncology alone and an overall clinical trial enrollment of more than 6000 patients a year.

And, the center is among the nation’s premier research hubs, which includes serving as an NCI-designated consortium for the growing Mountain State region and as a principal site for developing emerging therapies for patients with lung cancer.

These milestones have been reached in no small measure thanks to the efforts of Bunn, who served as the center’s first director for more than 20 years. Yet Bunn’s impact upon cancer care extends far beyond the programs he helped build in Colorado.

Over the years, Bunn has served as president of the American Society of Clinical Oncology (ASCO), the International Association for the Study of Lung Cancer (IASLC), and the Association of American Cancer Institutes, and as chairman of the FDA’s Oncology Drugs Advisory Committee. He was the federal government’s principal expert witness in the United States of America v Philip Morris USA, the landmark legal battle against the tobacco industry in the 2000s.

And, the research team he helped build at the University of Colorado Cancer Center has investigated many of the new therapies approved in recent years for patients with lung cancer.

In recognition of his achievements, the Giants of Cancer Care® advisory board honored Bunn in May as the 2014 winner for Lung Cancer.

From his vantage point, Bunn takes an optimistic view of the progress that has been made against lung cancer during his career. “When I was a young man, we did trials in non—small cell lung cancer [NSCLC] at the NCI with 12 drugs in a row that no one responded to,” Bunn recalled in an interview. “The median survival at the time was 5 months. That was grim. Now, if you have a molecular driver, the chance that a pill will bring you benefit is about 80%. The average survival of those patients is 3½ years. “So if you said to somebody, ‘You’re going to die in 3½ years,’ it might not make them very happy—rightfully so,” Bunn continued. “But if you said that a few years ago it would have been 5 months and that now it’s 3½ years, you would say that some of our investment in cancer research is paying off.”

A Push Toward Oncology

At the same time, Bunn sees many remaining challenges. “Making the cure rate higher is a major unmet need,” he said, as is improving the time for moving new treatments into curative settings.If it had not been for the Vietnam War, Bunn might never have explored a career in oncology research.

In 1971, shortly after the expiration of the education deferment that allowed young men to avoid the draft, Bunn obtained his medical degree from Cornell University Medical Center in New York City.

“When I was in medical school, I knew that I wanted to do something with internal medicine, but I didn’t know what,” Bunn said. He discussed his options with one of his professors, Richard T. Silver, MD, who today is director of the Leukemia and Myeloproliferative Center at New York Presbyterian-Weill Cornell Medical Center. Earlier in his career, Silver had worked at the NCI.

“When I suggested to him that I was interested in research and I was not interested in Vietnam, he said you could kill two birds with one stone and go to the National Cancer Institute, be in the public health service, meet your military obligation, and do research,” related Bunn.

After an internship and residency at HC Moffitt Hospital at the University of California, San Francisco, Bunn was able to do just that. He prevailed amid stiff competition to land a position as a clinical associate in the NCI’s Medicine Branch under the direction of Vincent T. DeVita Jr, MD, a 2013 Giants of Cancer Care award winner, and others.

For Bunn, it was the beginning of a quest to understand the biological and molecular underpinnings of cancer. He concentrated on preclinical studies delving into the biology of lung cancers and cutaneous T-cell lymphomas with many mentors and colleagues.

The Move to Colorado

Notably, Bunn’s work at the NCI frequently involved the use of what were then new technologies such as cell cultures to establish new cell lines and flow cytometry to analyze their DNA.Bunn advanced to become head of the Cell Kinetic Section at the NCI, but after 11 years he felt it was time to choose between spending his career in the public health sector and pursuing other options. “I was looking for an academic place that wanted to build a first-rate cancer center that would be a good academic program and a good place to raise a family,” Bunn related. So he accepted a position as head of the Division of Medical Oncology at the University of Colorado Cancer Center in 1984. Three years later, he also became the center’s first director, a position he held until 2009.

In many ways, the changes that have transformed the care provided at the center reflect those that took place throughout the field. “At the time, the infusion center had two chairs,” Bunn recalled of his arrival in Colorado. “One oncology nurse more or less mixed and administered the chemotherapy. Now, there are more than 60 infusion chairs.”

Such growth, Bunn said, “is not only true in Colorado, it is true in many places. Oncology care is way different than it used to be. There has been a tremendous amount of growth and a tremendous amount of subspecialization.”

Under Bunn’s leadership, that growth in Colorado has produced one of the nation’s most successful lung cancer research programs. The key ingredients, Bunn said, include “basic scientists who are interested in lung cancer and preclinical models, and pathologists who are interested in biomarkers and molecular analyses.” There are other important players: pulmonologists,radiologists, and translational researchers. Bunn himself has coauthored more than 300 peer-reviewed journal articles and more than 300 conference abstracts, and has written or coauthored nine books and about 90 book chapters. Asked to cite his most important research milestone, Bunn noted the development of the “biomarker concept” in NSCLC.

Starting in the late 1990s, Bunn and colleagues explored multiple biomarkers for molecularly targeted therapies for NSCLC. Their work aided in the development of EGFR tyrosine kinase inhibitors for patients with that mutation, originally with gefitinib (Iressa) and later with erlotinib (Tarceva), which the FDA approved for patients with NSCLC in 2003 and 2004, respectively.

The evolving understanding of the biology of lung cancer has enabled clinicians to move beyond the more toxic chemotherapy regimens that were formerly standards of care. “In the past, what we did had no scientific basis,” said Bunn. “Now, we’re only beginning to harness the immune system and these molecular drivers, and it’s all based on science. I’m optimistic that in the next decade we can make more advances than we did in the past decades.”

Leading the Way

In the oncology community, Bunn and the program he helped establish are leading players in national and international research circles.

In 1992, the University of Colorado Cancer Center was awarded the federal government’s first Specialized Program of Research Excellence (SPORE) grant in lung cancer. The grant, which totaled $2.4 million last year alone, has been funded every year since then and is believed to be the longest continuous SPORE project. Currently, Bunn serves as principal investigator for the SPORE lung cancer grant, which includes four major projects involving early detection, chemoprevention, novel treatments, and resistance to EGFR inhibitors.

Family’s Influence at Work

The center was among the largest contributors to the National Lung Screening Trial, which culminated in 2013 in new guidelines endorsing the use of low-dose CT screening for people ages 55 to 80 at high risk for developing lung cancer. And, the center’s Fred R. Hirsch, MD, PhD, a translational researcher who explores biomarkers, is serving as a co-chair for the recently launched Lung-MAP trial. Throughout his career, Bunn has received many honors, including a leadership award from the American Association of Cancer Research and the IASLC in 2010, given at the first Molecular Origins of Lung Cancer conference; the Caine Halter Hope Award in 2012; the IASLC Merit Award in 2003; and the American Italian Cancer Research Foundation Award in 2002. He became the 71st Distinguished Professor in the history of the University of Colorado system in 2013.At first glance, the arc of Bunn’s career might seem unsurprising. His father, Paul A. Bunn, MD, was a respected infectious disease specialist who became one of the first full-time professors at Syracuse University and a civic-minded resident of the nearby town of DeWitt, New York, where he raised his family. Members of Bunn’s extended family also were physicians. Bunn was impressed by his father’s dedication to medical ethics. He recalled that his father contracted tuberculosis as a result of treating patients as a medical student and had little patience in later years with doctors who did not want to care for individuals with HIV. His father’s philosophy, and one that Bunn shares, is “If you’re a physician, the Hippocratic Oath says anybody who comes into your house, you’re going to take care of.” Yet when Bunn entered Amherst College, he did not plan to follow in his father’s footsteps and instead intended to pursue political science. He changed his mind, though, after he did well in required math and science courses, and ended up graduating in 1967 with a Bachelor of Arts in biology.

Like his father, Bunn also has displayed a community spirit in his approach to lung cancer research. In addition to his full-time academic positions at the University of Colorado Cancer Center and a 10-year tenure as IASLC executive director, Bunn has held what he calls “volunteer administrative jobs.”

He was president of ASCO from 2002 to 2003, of IASLC from 1994 to 1997, and of the American Association of Cancer Institutes in 1996. He also chaired the FDA’s Oncology Drug Advisory Committee from 1992 to 1996.

These days, Bunn has stepped back from his various administrative roles partly so that he has more time to spend with his family. “One’s family is the most important thing in one’s life,” said Bunn. “It is a difficult balancing act. Fortunately, I have three wonderful children, a wonderful wife, and four terrific grandkids. It is one of the reasons not to have administrative jobs right now.”

Although his schedule might not be quite as packed these days, Bunn still serves as a faculty member at the University of Colorado School of Medicine and as principal investigator for the SPORE grant; he also still treats patients, including individuals diagnosed with cutaneous T-cell lymphoma.

As far as his research goals are concerned, his plans are straightforward and succinct: “My future research goals would be to develop better treatments for lung cancer patients,” he said. “That hasn’t changed.”

Bunn Hailed as Leader on the World Stage

Fred R. Hirsch, MD, PhDCEO, International Associationfor the Study of Lung Cancer (IASLC)Professor of Medicine and PathologyUniversity of ColoradoAurora, CO

“Dr Bunn is a true leader in thoracic oncology and has, over several decades, initiated one innovative project after the other. He is not only a leader, but also a wonderful mentor for many next-generation thoracic oncologists.

“I don’t know anyone who knows so much about everything in thoracic oncology as Dr Bunn, and it is a privilege to learn from him on a daily basis. For IASLC, Dr Bunn has been instrumental in bringing this organization to the level of being the leading multidisciplinary international organization in thoracic oncology.”

John Minna, MD Director, Hamon Centerfor Therapeutic Oncology ResearchCo-Director, ExperimentalTherapeutics ProgramSimmons Cancer CenterUT Southwestern Medical CenterDallas, TX

“Besides all of Paul’s scientific contributions in the clinic and laboratory toward the treatment of lung cancer, perhaps his accomplishment that will have the largest global impact is the monumental work he did through the IASLC and related efforts.

“In these, he brought the worldwide lung cancer clinical and translational research community to work together, and importantly, to work together at the cutting edge of research. In this way, Paul’s work became synergistic, where the whole was much greater than the sum of the parts.” .

Dr. Bunn's Selected Papers

• Levy BP, Chioda MD, Herndon D, et al. Molecular testing for treatment of metastatic non-small cell lung cancer: how to implement evidence-based recommendations [published online September 1, 2015]. Oncologist. pii:theoncologist.2015-0114.
• Pekar-Zlotin M, Hirsch FR, Soussan-Gutman L, et al. Fluorescence in situ hybridization, immunohistochemistry, and next-generation sequencing for detection of EML4-ALK rearrangement in lung cancer [published online February 26, 2015]. Oncologist. 2015;20(3):316-322.
• Hirsch FR, Bunn PA Jr. Progress in research on screening and genetics in lung cancer [published online December 23, 2013]. Lancet Respir Med. 2014;2(1):19-21.
• Bunn PA Jr, Franklin W, Doebele RC. The evolution of tumor classification: a role for genomics? Cancer Cell. 2013;24(6)693-694.
• Hirsch FR, Bunn PA Jr. A new generation of EGFR tyrosine-kinase inhibitors in NSCLC [published online March 26, 2012]. Lancet Oncol. 2012;13(5):442-443.
• Hirsch FR, Kabbinavar F, Eisen T, et al. A randomized, phase II, biomarker-selected study comparing erlotinib to erlotinib intercalated with chemotherapy in first-line therapy for advanced non-small-cell lung cancer [published online August 11, 2011}. J Clin Oncol. 2011;29(26): 3567-3573.
• Hirsch FR, Herbst RS, Olsen C, et al. Increased EGFR gene copy number detected by fluorescent in situ hybridization predicts outcome in non-small-cell lung cancer patients treated with cetuximab and chemotherapy. J Clin Oncol. 2008;26(20):3351-3357.
• Bunn PA Jr, Dziadziuszko R, Varella-Garcia M, et al. Biologic markers for non-small cell lung cancer patient selection for epidermal growth factor receptor tyrosine kinase inhibitor therapy. Clin Cancer Res. 2006;12(12):3652-3656.
• Bunn PA Jr, Helfrich B, Soriano AF, et al. Expression of Her-2/neu in human lung cancer cell lines by immunohistochemistry and fluorescence in situ hybridization and its relationship to in vitro cytotoxicity by trastuzumab and chemotherapeutic agents. Clin Cancer Res. 2001;7(10):3239-3250.
• Kelly K, Crowley J, Bunn PA Jr, et al. Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non--small-cell lung cancer: a Southwest Oncology Group trial. J Clin Oncol. 2001;19(13):3210-3218.
• Pisters K, Kris M, Bunn PA Jr, et al. Induction paclitaxel/carboplatin in early stage non-small cell lung cancer. Bimodality Lung Oncology Team. Semin Oncol. 1997;24(4 Suppl 12):S12-41-S12-44.
• Hazuka MB, Crowley JJ, Bunn PA Jr, et al. Daily low-dose cisplatin plus concurrent high-dose thoracic irradiation in locally advanced unresectable non-small-cell lung cancer: results of a phase II Southwest Oncology Group study. J Clin Oncol. 1994;12(9):1814-1820.