Real World Health Care Blog

Non-Small Cell Lung Cancer

Non-Small Cell Lung Cancer: EGFR Mutations and Targeted Therapies

For the next several weeks, Real World Health Care will take a brief hiatus as we re-publish some of our most popular interviews on oncology-related topics.

The editors of Real World Health Care, along with our sponsor, the HealthWell Foundation, understand that cancer takes a huge toll on patients, their families and loved ones. About 1.6 million new cases of cancer were diagnosed in the United States last year, and nearly 600,000 people died from the disease.

Real World Health Care is pleased to shine a spotlight again on the researchers, clinicians and organizations dedicated to the future of cancer care. We also are proud of the work being done by the HealthWell Foundation, which provides a financial lifeline to underinsured Americans through grants for cancer patients across a variety of funds, such as multiple myeloma, bone metastases, and chronic myeloid leukemia for Medicare patients, to help them afford the medical treatments they so desperately need.

Continuing our series on non-small cell lung cancer, this week Real World Health Care speaks with Lecia V. Sequist, MD, MPH, Associate Professor of Medicine at Harvard Medical School and the Mary B. Soltonstall endowed chair in oncology at Massachusetts General Hospital. Dr. Sequist’s research focuses on studying novel targets and targeted agents for lung cancer treatment, particularly those that target the epidermal growth factor receptor (EGFR) and in detecting and studying the significance of tumor cells circulating in the bloodstream.

Real World Health Care: Tell us about what you do at Massachusetts General Hospital, especially in relation to research and treatment of non-small cell lung cancer.

Lecia V. Sequist, MD, MPH, Harvard Medical School

Lecia Sequist: I’m a medical oncologist with a busy practice, seeing and treating patients with lung cancer. I also conduct clinical and translational research on new drugs, looking at the molecular aspects of tumors and biopsies as patients go through various forms of treatment. My focus is on personalizing treatment for each patient.

RWHC: Can you share some highlights of your recent research in non-small cell lung cancer?

LS: Most of my recent research has revolved around EGFR mutations. One of the biggest advances in lung cancer in recent years is that we’ve come to understand lung cancer is not one disease. It’s many diseases. We can now tell the difference between one cancer and another by looking at the tumor genetics. These are not the genes we inherit from our parents, rather they are genes that reside only in cancer cells. These genes are at the core of what causes cancer. By identifying these genes in a lung cancer patient’s tumor, we can be more successful with treatments that target those genes and the proteins they produce.

EGFR mutations were first discovered here at Mass General, right around the time I started in oncology. It was a very exciting time, and ushered in a new era of personalized treatment for cancer. Since those early days, we’ve done a tremendous amount of research with patients who have the EGFR mutation, and we’ve found treatments that work better than standard chemotherapy.

RWHC: What are some of the biggest challenges you face as a researcher studying non-small cell lung cancer?

LS: I think of the challenges in two categories: scientific and societal. From the scientific point of view, we can’t currently identify mutations in every lung cancer, though we’re constantly working to uncover more of them. The group of lung cancer patients who have no identifiable mutation, or who have a mutation with no matching drug therapies at this time, are effectively left out of the “molecular revolution.” For those groups, the challenge is to find alternative approaches. Luckily some of the newer immunotherapies may work particularly well in such patients. Then down the road, we know that targeted therapies eventually “wear off,” in the sense that cancer cells get smart and find ways to work around the roadblocks we put in their path. For example, we saw this with the first generation of tyrosine kinase inhibitors (TKIs) developed to target EGFR mutations. Most patients initially responded, but subsequently developed a resistance after about a year, because they developed a second mutation that prevents the TKIs from binding to the cancer cells. Last year, a new EGFR drug was FDA approved that is able to effectively target this second mutation. Now we’re racing trying to learn how the cancers may get around the newer drug and also looking at strategies to prevent resistance.

From a societal standpoint, one of our biggest challenges in the lung cancer research community is the stigma that still exists around lung cancer. In the United States, we were fortunate to have had a very successful public health campaign around the dangers of smoking over the last generation. Those dangers are important to understand, but one of the unexpected consequences of this was to popularize the opinion that lung cancer is a self-inflicted disease and therefore patients carry some degree of blame. Not only does this end up negatively affecting individual patients, it also cuts into research funding. The fact is, some smokers get lung cancer while others don’t. And more importantly, many lung cancer patients have never smoked. No one deserves lung cancer and research must push forward to stop this, the deadliest of all cancers.

RWHC: What are some of the biggest challenges you face as a clinician treating patients with non-small cell lung cancer?

LS: There are promising treatments being studied in clinical trials, but many patients don’t have access to those treatments because the trials are concentrated in academic centers. Even if patients have geographic access to research studies, clinical trials have fairly high thresholds for eligibility, so if a patient has other medical conditions — which many lung cancer patients have — or if their cancer has certain characteristics, they won’t be eligible for the trial. We need to keep pressure on the pharmaceutical industry to include broader groups of patients in trials so all patients can get access to promising new treatments.

RWHC: What do you think are some of the biggest opportunities for advancement in how we research non-small cell lung cancer and treat people with the disease?

LS: Immunotherapy has really changed the paradigm for non-small cell lung cancer. Years of failed vaccine studies led us to believe that it wasn’t possible to affect the human immune system in meaningful ways against lung cancer. Now that we’ve hit upon a different way to activate the immune system, new discoveries are tumbling out the door every day. Unlike past treatments, immunotherapy has true promise for long-term disease control. There are already three FDA-approved lung cancer immune therapy treatments over the last year and likely many more to come. I think someday we’ll look back on this time and say that this is when the needle really started to move.

RWHC: Why did you get into this field of research? What continues to inspire you?

LS: I was initially drawn to studying lung cancer when I was in training by the doctors who were mentoring me and the patients I met. At the time, there weren’t many treatments available for non-small cell lung cancer, so there was a lot of room for improvement. This was attractive to me as a clinician and a researcher and it has remained a vibrant and ever-changing field. I enjoy being involved in the exponentially increasing number of treatments available and how these new treatments can bring hope to patients. It has ended up being an intellectually stimulating and extremely fulfilling career and I continue to be inspired by the patients I meet every day.

American Lung Association: Research Focused on Improving Patient Care and Saving Lives

For the next several weeks, Real World Health Care will take a brief hiatus as we re-publish some of our most popular interviews on oncology-related topics.

The editors of Real World Health Care, along with our sponsor, the HealthWell Foundation, understand that cancer takes a huge toll on patients, their families and loved ones. About 1.6 million new cases of cancer were diagnosed in the United States last year, and nearly 600,000 people died from the disease.

Real World Health Care is pleased to shine a spotlight again on the researchers, clinicians and organizations dedicated to the future of cancer care. We also are proud of the work being done by the HealthWell Foundation, which provides a financial lifeline to underinsured Americans through grants for cancer patients across a variety of funds, such as multiple myeloma, bone metastases, and chronic myeloid leukemia for Medicare patients, to help them afford the medical treatments they so desperately need.

As part of our series on non-small cell lung cancer (NSCLC), Real World Health Care spoke with Susan J. Rappaport, MPH, vice president for research and scientific affairs, American Lung Association. Rappaport provides leadership and direction in the development and implementation of the American Lung Association public health education and research programs. She works with leading scientists to develop research and scientific policies relevant to lung disease.

Here, Rappaport shares insights on how the American Lung Association supports research for NSCLC and other types of lung cancer.

Real World Health Care: How does the American Lung Association fund, or acquire funding, for the research it supports?

Susan J. Rappaport, MPH, American Lung Association

Susan Rappaport: The American Lung Association has been funding research for more than 100 years. We receive our support through public donations, including our annual Christmas Seals® campaign, Fight for Air Climbs and LUNG FORCE Walks. We have a long history of connecting with people and communities in support of lung health.

Our organization was founded in response to tuberculosis — the most feared disease at that time. Now, with tuberculosis largely controlled in the United States, we have turned our sights toward defeating lung cancer and working toward a world free of lung disease.

Research is a critical part of our LUNG FORCE initiative, which focuses on lung cancer in women, to raise awareness and more lung cancer research funds. Through LUNG FORCE, we have already invested an additional $1 million in lung cancer research. The Lung Association’s Awards and Grants Program supports a rich array of studies in lung cancer to help improve methods of early detection and develop better treatment options for patients. In the past four years, we have funded more than $4 million in lung cancer research grants and have doubled our investment in lung cancer since 2015. This year, the Lung Association is funding more than $6.5 million in lung disease research.

RWHC: How does the Lung Association determine what research it supports, either through direct funding or through its advocacy work?

SR: It is important to the Lung Association that we fund the best projects available on a host of lung disease issues. We solicit grant applications each year, and successful applicants are identified through a scientific peer review committee system modeled on the one used by the National Institutes of Health (NIH). These peer review committees are comprised of accomplished and diverse researchers with the necessary expertise to review and assess each proposal. Proposals are funded based on the results of this process, ensuring that we only fund those applications considered of the highest quality, and with the best chance to advance our understanding of diseases, improving patient care and ultimately saving lives.

We know our chances of significant improvement in patient lives and of finding a cure increase when we work together. That’s why we collaborate with other organizations and advocate for increased research funding at NIH.

RWHC: What is the Lung Association currently doing to promote and/or fund research into NSLC? What are your priorities in this area?

SR: Our overall priority is to fund the best research that has the greatest chance of a scientific breakthrough and making a difference in patient care and quality of life. With increased funds available to lung cancer researchers, we attract and retain brilliant, motivated investigators to the field.

As NSCLC accounts for 85 percent of all lung cancer cases, many of the proposed projects do focus on this specific issue. However, the nature of scientific discovery has shown us that answers from one area of research can also work more broadly. Areas that drive our lung cancer research — all of which can address NSCLC — include:

  • Development of new and combination therapies
  • Biomarker discovery and validation
  • Targeted therapies and resistance
  • Screening implementation and novel screening for the non-high-risk population
  • Lung cancer initiation and growth

RWHC: What are the biggest challenges in NSCLC research and how is the Lung Association working to overcome them?

SR: Among our biggest challenges is to be able to fund all the qualified research applications we receive. Each year, we turn away qualified researchers and projects due to the limited availability of funds. LUNG FORCE seeks to raise additional funds for lung cancer research and raise awareness about lung cancer as the leading cause of cancer deaths. Again, we strive to overcome gaps in funding by leveraging our resources, collaborating with other organizations and advocating for increased federal funding for lung cancer research.

RWHC: What would you say have been the most important advances in NSCLC treatment over the past 10 years?

SR: Scientists have discovered somatic mutations — called “driver mutations” — that drive the development of lung cancer. These discoveries, made over the past decade, have transformed how to identify and treat the disease. Now, lung and other tumors can be tested for these mutations.

There are now specific therapies that can address those genetic changes that keep the cancer cell growing. These therapies target the mutations in different ways, are more specific and have fewer side effects. These advances in precision medicine have led to lifesaving discoveries and treatments.

Another sea change in lung cancer treatment is immunotherapy. Cancer cells have found ways to keep the immune system from identifying and destroying them, as they do for infectious invaders. Immunotherapy medicines work to activate a person’s own immune system to recognize and kill cancer cells. So far, immunotherapy has only been approved to treat some forms of NSCLC. Currently, only a minority of patients respond to immunotherapy. However, a large proportion of those who do respond have improved survival.

RWHC: What do you think will be the next biggest advance in NSCLC treatment in the near future?

SR: Our scientific advisors believe that the Lung Association should invest in the following areas, which they identified as having the potential for the most important breakthroughs — all of which can apply to NSCLC:

  • Additional precision medicine in treatment of early-stage lung cancer
  • Precision medicine to identify patients who would benefit from newly developed lung cancer screening, irrespective of smoking history
  • Non-invasive biopsy strategies
  • Comparative effectiveness studies to improve clinical outcomes and cost-effectiveness after treatment

RWHC: Does the Lung Association’s LUNG FORCE research innovation project address NSCLC?

SR: This award will address all types of lung cancer. To better understand the impact of lung cancer in women, the American Lung Association has created a new research award to examine gender differences in lung cancer. Sharad Goyal, M.D., is the first-ever recipient of the LUNG FORCE Research Innovation Project: Lung Cancer in Women Award.

Dr. Goyal’s project focuses on ionized radiation exposure during common cardiology procedures and how that affects the risk of developing lung cancer for women. The project leverages two large population-based data sets that include both cancer and cardiac information. Through analyses of these data sets, Dr. Goyal will evaluate the factors influencing the relative risk of developing lung cancer in a diverse group of people after this type of radiation exposure. This has not been previously studied, and it will take two to three years to complete the analysis.