October 2015, Vol. 4, No. 5

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Looking into the Future of Lung Cancer Research

Fred R. Hirsch, MD, PhD

16th International Lung Cancer Congress

Each year, the Bonnie J. Addario Lung Cancer Foundation (ALCF) recognizes luminaries in the quest to cure lung cancer with the Addario Lectureship Award. This year, Fred R. Hirsch, MD, PhD, Professor of Medicine and Pathology, University of Colorado School of Medicine, Denver, delivered his keynote lecture on the many challenges facing researchers and clinicians in the field.

Despite the progress being made in the treatment of lung cancer, an increasing number of younger females and never-smokers are suffering from the disease. As Hirsch discussed in his keynote lecture at the 16th Annual International Lung Cancer Congress, lung cancer is no longer an exclusively smoking-related disease.1

“In order for progress to occur, we need to focus on improving survival and reducing burden,” said Hirsch, “but we also need to understand why never-smokers and younger females get lung cancer in the first place. The Genomics of Young Lung Cancer Study, supported by the ALCF, will provide us lots of new information around this problem.”

Advances in Screening and Detection

Screening for lung cancer is an area that has seen significant developments, especially in the past 8 years. As Hirsch cautioned, however, a great deal of work remains to be accomplished.

“We need to keep in mind that [the] false-positive rate of screen-detected nodules is more than 90%,” he said. “How do we reduce that? We don’t know yet what a screening of never-smokers should look like at this stage.”

One radical solution for detection, proposed by Hirsch, is a gold nanoparticle assay that can detect very small volatile organic compounds. Odor and medicine have long been linked together, and the proposed technology would function like an explosive-sniffing dog—only detecting cancer instead of bombs.

“High-risk individuals blow into a balloon through a specially designed tube,” Hirsch explained, “and then we analyze the air in the balloon. Our very preliminary data show that this technology can distinguish well between benign and malignant nodules.”

Improving Drug Development

Although there has been tremendous progress in the treatment of lung cancer over the past decade, including several new and powerful drugs approved in the United States and around the world, Hirsch stressed the importance of improving drug development.

“Faster identification of effective drugs, faster approval and identification of companion diagnostics, is critical,” Hirsch emphasized. “The key is that you have a unique partnership between the different stakeholders—the FDA, industry, academia, and co-operative groups. That is what makes those initiatives so important; it makes it easier to quickly identify new drugs and get them rapidly approved and not waste 10 to 15 years.”

Immunotherapy Brings Hope for the Future

Immunotherapy is the focus of two-thirds of discussions at conferences these days, said Hirsch, and the mechanisms are now well understood.

Data from the CheckMate 057 trial for nivolumab, presented at the 2015 Annual Meeting of the American Society of Clinical Oncology, showed very encouraging 1-year progression-free survival, 1-year overall survival, and long-term overall survival for patients with nonsquamous non–small cell lung cancer.2

“The data show that we are absolutely on the right track,” said Hirsch. “The same for pembrolizumab. This is the platform we need to build on in the future.”

Despite the strides being made, however, immunotherapy also poses unique biological challenges.

“We need to look into combination therapy,” he said, “but combinations should be based on biological evidence, so we need to learn more about resistant mechanisms or mechanisms of action.”

According to Hirsch, molecular assays and therapeutic regimens also need to be harmonized.

“We cannot exist with 4 different drugs having 4 different assays,” he said. “We have a tendency to focus on 1 single platform, 1 single marker, but composite predictive biomarkers should be used in the future.”

Biomarkers are the center of everything—risk assessment, screening, prevention, diagnosis, and drug development—but standardization and validation need to be considered, Hirsch maintained.

“Why don’t we have an Oncotype DX or a MammaPrint in lung cancer? In my opinion, we have a lot of potential candidates, but they have not yet been fully validated and standardized,” Hirsch concluded.

References
  1. Hirsch FR. Eighth Annual Addario Foundation Keynote Lecture: looking into the future of lung cancer research. Presented at: 16th Annual International Lung Cancer Congress; July 30-August 1, 2015; Huntington Beach, CA.
  2. Paz-Ares L, Horn L, Borghaei H, et al. Phase III, randomized trial (CheckMate 057) of nivolumab (NIVO) versus docetaxel (DOC) in advanced non-squamous cell (non-SQ) non-small cell lung cancer (NSCLC). J Clin Oncol. 2015;33(suppl). Abstract LBA109.
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