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Tag Archives: targeted therapy

Profiling Melanoma to Predict Immune Therapy Success

May is Melanoma awareness month, and our series on melanoma continues with a discussion with Dr. Douglas B. Johnson of the Vanderbilt-Ingram Cancer Center. Dr. Johnson leads Vanderbilt’s melanoma clinical and research program, overseeing clinical trials, patient care and translational research. His research interests focus on developing new immune and targeted therapies for melanoma, and in using existing treatments in the most effective ways. Specifically, he is exploring ways to profile cancers to predict which patients will benefit from immune therapies.

Combination and Targeted Therapies Allow Long-Term Survival

Real World Health Care: You published a review of therapeutic advances and treatment options in metastatic melanoma. Can you summarize the review and discuss its implications for patients with the disease?

Dr. Douglas Johnson, Vanderbilt-Ingram Cancer Center

Douglas Johnson: Treatment options for advanced melanoma have been rapidly advancing. We now have multiple options for patients with this disease, when even 5-10 years ago very few existed. Immune therapies, which unleash the immune system against the cancer, result in long-lasting responses in a large fraction of patients. The number of patients who benefit from treatment increases when two immune therapy treatments are combined, although at the cost of increased side effects. Targeted therapies, which block the effects of particular genetic mutations, have also made a big difference, particularly for patients who have mutations in the gene BRAF, which represents about half of melanoma patients. These treatments have transformed a disease which was essentially uniformly fatal to one that is often associated with long-term survival.

RWHC: Are you currently working on any new studies or trials relating to melanoma?

DJ: We have a number of combination immunotherapy trials. These types of trials are attempting to use strategies that extend the benefits of immune therapy to more patients. We are also working on developing biomarkers for immune therapy responses. In particular, we are evaluating whether the number and types of mutations in melanoma, as well as the expression of particular immune proteins, can predict which patients will respond to immune therapy. We also are studying the side effects and toxicities of immune therapy, to understand why they occur, who is affected, and develop effective prevention and treatment strategies.

Melanoma Research and Treatment 

RWHC: What do you see as the most promising treatments on the horizon for melanoma?

DJ: A number of promising immune therapy combinations are being developed. It is very difficult to say which is the most promising, but likely some combination of anti-PD-1 therapy with other immune or targeted therapy agents.

RWHC: What are the biggest challenges facing melanoma researchers?

DJ: One of the biggest challenges is predicting who will respond to current immune and/or targeted therapies so we can assign the right treatment to the right patient. Researchers also are challenged to develop the most effective combination therapies and to prevent and manage toxicities. In some ways, the development of effective therapies has made it more difficult to enroll patients in clinical trials. This is a good problem to have, but it limits the speed of developing new effective therapies.

RWHC: What are the biggest challenges facing clinicians treating patients with melanoma?

DJ: From a clinical standpoint, the challenges are similar. Despite the current advances, there is still a large subset of patients who do not respond well to treatments. We need to understand who those patients are upfront, and develop more effective treatment strategies for them.

Toxicities are also a major consideration, particularly for patients with other medical problems or who have limited functional status. It is always a difficult balancing act deciding between single agent and combination immune therapy. On one side is the potential for a somewhat higher response rate, on the other side is the significant increase in side effects (which are typically manageable). Every clinician and patient has a different threshold regarding when to offer these therapies.

Improving the Lives of Melanoma Patients

RWHC: What initially interested you in studying and treating melanoma? What continues to inspire you?

DJ: I had a friend during my medical training who developed stage III melanoma and I was struck by the lack of treatment options at the time. When I joined Vanderbilt, my mentor Dr. Jeff Sosman was doing amazing research, and I become very excited about the prospect of doing groundbreaking research that would affect patient lives. That approach continues to drive and inspire me.

Lung Cancer Alliance Moves Research Forward Through Innovative Partnerships

This week, Real World Health Care speaks with Jennifer King, Ph.D., Director of Science and Research for the Lung Cancer Alliance. The Lung Cancer Alliance is the leading and highest rated nonprofit organization dedicated to fighting lung cancer in the nation. Since 1995, it has played a critical role in every major advance — changing how people support, talk about, detect and treat the disease — and turning those impacted into survivors. Its mission is saving lives and advancing research by empowering those living with and at risk for lung cancer.

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

Jennifer King, Lung Cancer Alliance

Jennifer King, Lung Cancer Alliance

Jennifer King: Our funding for all our programmatic work, including our research platform, comes from a variety of sources. The majority is through individuals, private family foundations and corporate partnerships. On the research side of things, we also apply for grant funding, including through federal agencies like the National Cancer Institute.

RWHC: How does the LCA determine which research it supports, either through funding or through its advocacy work?

JK: Our research vision consists of six core areas: screening implementation, biomarker research, patient-powered research, enhancing clinical trial participation, survivorship, and increasing research capital. If a project or initiative fits in one of these six buckets, we will consider it for our portfolio. We don’t make direct grants; we work with researchers and other organizations to move projects forward through innovative partnerships.

RWHC: What is the LCA currently doing to promote and/or fund research into non-small cell lung cancer? What are your priorities in this area?

JK: We have funded a young investigator in partnership with the Conquer Cancer Foundation. Her work is currently focused on immunotherapy research for people with late stage NSCLC. We are also launching a clinical trials initiative to navigate more patients through the clinical trials process and enhance clinical research. There are so many emerging therapies in this area that more clinical research is necessary to understand what the right treatments are at the right time for individual patients.

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

JK: A big challenge is the lack of research capital. We fund young investigators, as I mentioned, to support more people studying lung cancer. We also work with Congress to ensure the continued funding of the Lung Cancer Research Program with the Congressionally Directed Medical Research Program at the Department of Defense. To date, $102 million has been allocated for lung cancer research through this program.

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

JK: Without a doubt, the two biggest advances have been targeted therapies and immunotherapies. Targeted therapies attack a specific mutation in the cancer cells. This typically causes fewer side effects than standard chemo and truly personalizes the treatment plans for each person diagnosed. Immunotherapies use a patient’s own immune system to fight his or her cancer. There have been a number of new drugs in both fields that are offering more hope to patients, but a lot of questions remain about how to best use the new therapies.

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

JK: We are on the horizon of understanding how to combine different types of NSCLC treatments and for whom. There are trials using immunotherapies and targeted therapies with each other, as well as with chemo, radiation, and surgery. A huge number of questions remain about how to use these drugs, for whom, and together or in what sequence. Understanding how the new agents do and don’t work together and being able to personalize the treatments for each individual cancer will lead to major changes in how we care for NSCLC patients. There are also exciting new advances in fields like nanotechnology and health information technology that may someday have a broad impact on cancer care.

RWHC: Why did you get into this field in the first place? What continues to inspire you about it?

JK: I have always been interested in the science of how disease works and how we can potentially use that knowledge to help patients. This started back in high school when I did a biology project on gene therapy. I’m a former cancer researcher, but I joined Lung Cancer Alliance in early 2015 because I was excited about seeing how the science was impacting the patients themselves.

It’s been such an inspirational 18 months. We had six new drugs approved in 2015 for lung cancer, and there’s many more on the way. The science is constantly changing as we keep learning, which keeps the work interesting. Now, I get to talk with patients, respond to questions and understand the issues that matter most to people living with lung cancer. It’s a constant inspiration to keep pushing for new and innovative research studies that will help patients and their families.