Lung radiography | Doctor examining a lung radiography

Cancer research is often defined by slow, incremental progress, building upon years, often decades, of previous discoveries. Then if we get lucky, someone figures out something that adds jet fuel to the process, propelling the entire field forward with new energy and new optimism. As chief of oncology at Yale and having cared for lung cancer patients for the past 25 years, I have never before seen such strides in the advancement of science for people suffering from lung cancer as we are seeing now. New targeted therapies and immunotherapies, as well as innovative protocol designs, are creating inroads into our understanding of this disease at a speed we?ve never experienced before.

An important reason for this sudden momentum is that multiple scientific investigations into lung cancer research are happening all over the world, many involving the use of immunotherapy — stimulating the body?s own immune system to attack tumor cells.

Photo 1.0: Roy S. Herbst, MD, PhD, is a principal investigator on the Stand Up To Cancer ? American Cancer Society Lung Cancer Dream Team.

Among a series of lung cancer presentations at this week?s annual meeting of the American Association for Cancer Research (AACR) was one simultaneously published online in The New England Journal of Medicine that exemplifies bench-to-bedside momentum and collaboration.[1]

Working together on the Stand Up To Cancer-Cancer Research Institute Cancer Immunology Dream Team, investigators from the Bloomberg-Kimmel Cancer Institute at Johns Hopkins in Baltimore and the Memorial Sloan Kettering Cancer Center in New York conducted a small, but compelling clinical trial in which lung cancer patients were given two doses of the immunotherapy drug nivolumab prior to having their lung tumors surgically removed.

The purpose of delivering the drug before surgery was not only to shrink the tumors, as is typically the goal of pre-surgical chemotherapy, but also to incite the patients? immune systems to target existing cancer cells before doctors began operating.

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Indeed, 45% of the patients in the trial responded so well that there was little evidence of the cancer remaining upon follow-up. In addition, the patients? immune systems also likely destroyed straggler tumor cells still circulating in the blood system, which can later take hold and lead to recurrence and metastasis.

As a consequence of this study, we may now have a path for surveillance and interception of rogue cancer cells after surgery, before they regroup and grow.

The caveat is that this was a small first-in-human clinical trial of 20 patients, and it has only been two years since these individuals underwent surgery. One of these patients has died of cancer recurrence. Since the baseline for measuring long-term survival is five years, it is important to follow trial participants before drawing conclusions regarding long-term survival.

The SU2C-CRI Dream Team has already embarked on several additional larger studies, which are essential before we can change the ?standard of care? for these patients. More studies incorporating other combinations may also be needed to find the best treatments. But for those of us who have been chipping away at lung cancer research for two decades, the chance to begin discussing and planning for the long-term survival of patients with metastatic lung cancer is, in itself, a major victory.

Lung cancer remains a worldwide scourge, claiming the lives of 1.6 million people a year. While tremendous progress has been made in extending the lives of people with breast cancer, non-Hodgkin?s lymphoma, and childhood leukemia, for example, the solutions to lung cancer have eluded our best and brightest researchers.

Two decades ago, only 5% of all lung cancer patients survived five years or longer. Today that average is around 18%. If caught and treated early, long-term survival chances are hovering around 56%. But once the cancer metastasizes, survival rates again plummet to five percent. Importantly, right now, about half of patients treated for early stage non-small-cell lung cancer will relapse and die of the disease due to recurrence and metastasis after surgery.

This discovery of a new way to use immunotherapy could become a game-changer for how cancer research should be conducted in the future. The key elements seem to be clinical care, teamwork, and innovation to intercept the natural course of cancer.

A significant part of the research funding came from a three-year US $ 10 million Dream Team grant from Stand Up To Cancer, which is focused on accelerating the pace at which new therapies get to patients, in collaboration with the Cancer Research Institute, dedicated to advancing immunotherapy to treat, control, and cure all cancers, as well as the National Cancer Institute, a federal agency that funds cancer research. (My own group has benefited at Yale from these funding sources).

There were certainly obstacles that had to be overcome:

  • Scientific advisors for both organizations had to agree that this cutting-edge and novel approach was worth financing.
  • Surgeons had to agree to be involved in the clinical trial, which meant changing their protocols to deliver immunotherapy first, slightly delaying surgery to remove the tumors.
  • Researchers at two institutions had to collaborate to develop biomarkers and new technologies for detecting whether and how many micrometastatic cells might still be lurking in the patients? systems.
  • Finally, patients with stage 1-3 lung cancers had to trust their physicians and muster the courage to become first-in-human enrollees in the clinical trial.

This study opens a floodgate of possibilities for the rest of us who work with lung cancer patients. Nearly every patient with lung cancer will receive immunotherapy treatment, but thus far with dramatic and lasting results in only about 20% of cases. Our challenge is to learn how to harness this power more effectively to reach broader patient populations and scientifically guide new combinations ? which is exactly what research groups across the country are doing and what our group at the Yale Cancer Center and 700 clinical sites in North America are doing as part of the Lung Cancer Master Protocol clinical trial.

If we can replicate what this Dream Team has found, if we can push the envelope even farther into understanding cancers of the lung, we may be able to ramp up long-term survival rates for a disease that has outfoxed us for more than a century. We may also extrapolate what we learn to improve patients? survival and quality of life for a number of other equally elusive cancers that continue to baffle us.

Much work still lies ahead of us, but given the results of this Dream Team of cancer scientists, today we have new research avenues to pursue and patients have new reasons to hope.

Last Editorial Review: April 16, 2018

Featured Image: Doctor examining a lung radiography Courtesy: ? 2010 – 2018 Fotolia. Used with permission. Photo 1.0: Roy S. Herbst, MD, PhD, Chief of Medical Oncology at the Yale Cancer Center and Smilow Cancer Hospital in New Haven, CT. Herbst, is a principal investigator on the Stand Up To Cancer ? American Cancer Society Lung Cancer Dream Team. Courtesy: ? 2010 – 2018 AACR/Stand Up to Cancer.? Used with permission.

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Roy S. Herbst, MD, PhD, is Chief of Medical Oncology at the Yale Cancer Center and chair of the AACR?s Tobacco and Cancer Subcommittee. He is nationally recognized for his leadership and expertise in lung cancer treatment and research. He is best known for his work in developmental therapeutics and the personalized therapy of non-small cell lung cancer, in particular the process of linking genetic abnormalities of cancer cells to novel therapies. Prior to his appointment at Yale, Herbst was the Barnhart Distinguished Professor and Chief of the Section of Thoracic Medical Oncology in the Department of Thoracic/Head and Neck Medical Oncology, at The University of Texas M.D. Anderson Cancer Center (UT-MDACC) in Houston, Texas. He also served as Professor in the Department of Cancer Biology and Co-Director of the Phase I Clinical Trials Program. After earning a B.S. and M.S. degree from Yale University, Dr. Herbst earned his M.D. at Cornell University Medical College and his Ph.D. in molecular cell biology at The Rockefeller University in New York City, New York. His postgraduate training included an internship and residency in medicine at Brigham and Women?s Hospital in Boston, Massachusetts. His clinical fellowships in medicine and hematology were completed at the Dana-Farber Cancer Institute and Brigham and Women?s Hospital, respectively. Subsequently, Dr. Herbst completed a M.S. degree in clinical translational research at Harvard University in Cambridge, Massachusetts. Herbst is a fellow of the American College of Physicians and an elected member of the Association of American Physicians. He is also a member of the medical advisory committee for the Lung Cancer Research Foundation and chair of the communications committee for ASCO and the International Association for the Study of Lung Cancer. He is currently the Vice Chair for Developmental Therapeutics for the Southwestern Oncology Group (SWOG) Lung Committee, Principal Investigator of the SWOG 0819 trial, and steering committee chair for the Lung Master Protocol (Lung MAP).