Emerging Reasons for Optimism in Lung Cancer

A Conversation With Paul A. Bunn, Jr, MD, FASCO

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Despite public smoking cessation initiatives and improved methods for early detection and treatment, lung cancer persists as the leading cause of cancer death in both men and women in the United States. However, over the past decade, smoking cessation efforts, increased screening, and new scientific developments in the fight against lung cancer have led to marked declines in incidence and mortality rates. To shed light on the current state of lung cancer, The ASCO Post spoke with lung cancer specialist and researcher Paul A. Bunn, Jr, MD, FASCO, Distinguished Professor and the James Dudley Chair in Cancer Research in the Division of Medical Oncology at the University of Colorado, Denver.

Scope of the Problem

Although the rate of smoking has decreased markedly over the past decades, about 15% of American adults currently smoke. Are we making enough progress in prevention and cessation initiatives for single-digit smoking percentages to be foreseeable in the future?

In the 1950s and 1960s, more than 50% of American men smoked and about 20% of American women smoked. Although we’ve made considerable progress in reducing that number, the goal is to get it to zero percentage of smokers. The good news is the percentage of male and female smokers has been declining steadily over the past decades, due largely to public actions such as awareness campaigns and restrictions on smoking indoors. One step the government could take, but has yet not, is to ban cigarette advertising.

Another newer threat is the rise of vaping, especially among younger individuals. In addition to tobacco carcinogens in vape smoke, there are other chemicals involved, which are part of the addictive process. There is also evidence showing that a percentage of people who vape ultimately become cigarette smokers. So, vaping is anything but an innocuous substitute for cigarette smoking.

Update on Early Detection

We still see a majority of patients with lung cancer presenting with late-stage disease. Please give us an update on early detection, such as spiral CT scanning in lung cancer.

As you know, the U.S. Preventive Services Task Force recently increased the number of patients eligible for computed tomography (CT) screening for lung cancer, dropping first-ever screening for at-risk people from age 55 to age 50. There is also an effort to increase lung cancer screening among minority and other disadvantaged groups. However, the reality is that only about 5% of people eligible for CT screening are, in fact, being screened. We need to increase that number dramatically if we want to see the real value of screening in those people who are at risk for lung cancer.

“We have seen better survival and quality of life outcomes in patients with lung cancer as a direct result of the Human Genome Project.”
— Paul A. Bunn, Jr, MD, FASCO

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Of course, the National Lung Screening Trial was conducted in the United States, but there were other international trials looking at lung cancer screening. In Europe, the NELSON trial results showed that CT screening reduced lung cancer mortality even more in women than in men. Some people have pointed out that the uptake in mammography in breast cancer screening began equally as slow as CT in lung cancer. So, there is hope among the lung cancer community that the same pattern will follow.

The majority of screened lung cancer cases are early stage and can be cured, which is a major reason we’re seeing the decline in lung cancer mortality among screened individuals. To continue the progress we’re seeing, we need to educate other physicians, including those in general practice, about the value of CT screening. Also, we need to educate and work with the community, including women’s organizations, to spread the word about the value of lung cancer screening.

Lung Cancer Research: The Human Genome Project and Beyond

In 2003, the Human Genome Project mapped, sequenced, and made publicly available the genetic content of human chromosomes. In lung cancer, has this knowledge translated into definable areas of diagnosis and treatment?

Let me back up a bit before the Human Genome Project. In the mid-1970s, despite the fact that lung cancer was the number one cause of cancer deaths in the United States, there was little research being done about its etiology. It was thought to be a self-induced disease, with stigma and pessimism playing a role in underfunding research efforts.

However, the Director of the National Cancer Institute at the time, Vince DeVita, Jr, MD, saw this disparity in funding and initiated a special branch of the Institute to increase lung cancer research. Led by Dr. John Minna with Dan Ihde, Adi Gazdar, Des Carney, myself, and others, this resulted in the development and characterization of a large array of lung cancer cell lines, which became the basis for many of the advances in therapy and biomarkers.

The Human Genome Project allowed study not only in patients with lung cancer, but in cell lines as well. Of course, that identified multiple specific driver mutations and molecular alterations, leading to the development of oral tyrosine kinase inhibitors. Those agents, along with immunotherapies, have led to increased survival for patients with lung cancer, as well as markedly reducing the toxicity we saw with previous treatments. So, we have seen better survival and quality-of-life outcomes in patients with lung cancer as a direct result of the Human Genome Project and increased lung cancer funding.

It’s important to note that we are still seeing benefits emerging from that and other work, which leads to genetic markers that can be treated with targeted therapies. Moreover, most of the decline in lung cancer mortality is a direct result of research that, like the Human Genome Project, has been funded by the government and the pharmaceutical industry.

Adjuvant Therapies After Surgical Resection

Minimally invasive surgical techniques have greatly improved. Please shed some light on the role of adjuvant therapies following surgical resection.

Surgery cures less than half of patients with lung cancer, but for those who are screened, surgery can cure up to 90% of patients with early-stage disease. The majority of the surgical failures are not a result of local tumor, but instead are from distant metastases present at the time of diagnosis.

So, the clinical question is, would systemic therapy given before or after surgery be able to eradicate the micrometastases and increase the cure rates? The answer is yes, systemic therapy in that setting works. There is a lot of ongoing research in detecting postoperative circulating tumor DNA, which would allow us to identify those who were cured by surgery, to avoid unnecessary adjuvant chemotherapy.

Right now, patients with stage IA lung cancer would undergo surgery alone. The cure rate for stage II and III disease has been shown to be increased by adjuvant systemic therapy, notwithstanding the side effects, which can be significant.

“The science is irrefutable: CT screening saves a considerable number of lives.”
— Paul A. Bunn, Jr, MD, FASCO

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For patients with genetic alterations, the question is whether tyrosine kinase inhibitors can increase cure rates without the need for chemotherapy. Similarly, for those patients without a genetic alteration, there’s the question of whether immunotherapy might be able to cure them without the need for chemotherapy or would add additional benefit when added to chemotherapy.

The advances in surgical and radiation therapy techniques have proved better and less toxic than prior therapies. Our hope is to develop systemic therapy that can be targeted to those who need it and at the same time reduce toxicity. When we see that evolution, the cure rates will increase even more in those who are not cured by surgery alone.

Moving Forward

Can you share with our readers your optimistic vision about lung cancer detection and treatment moving forward?

Despite the advances and better survival outcomes we’ve seen over the past decade or so, lung cancer remains the number one cause of cancer death in the United States. To increase cure rates, we need to ramp up our early detection screening efforts. The science is irrefutable: CT screening saves a considerable number of lives. However, the overriding goal should be a societal effort to reduce tobacco exposure and air pollution. Then, there’s the research component, which will accelerate our knowledge and ability to cure those patients with cancer who do not respond to current treatments. If we apply more resources to prevention and research, lung cancer will one day become a rare disease. 

DISCLOSURE: Dr. Bunn has served as a consultant or advisor to Ascentage Pharma, AstraZeneca/MedImmune, Bristol Myers Squibb, CStone Pharmaceuticals, Genentech/Roche, Imidex, Merck, and Viecure; and has received institutional research funding from Genentech.