This week, Real World Health Care continues our series on melanoma by interviewing two colleagues from the Rutgers Cancer Institute of New Jersey, a National Cancer Institute-designated Comprehensive Cancer Center.
Sharad Goyal, MD, is Associate Professor and Director of Clinical and Translational Research in the department of Radiation Oncology. He treats patients with brain tumors, melanoma and skin cancers, providing comprehensive cancer evaluation and the latest treatment planning technology to “map” tumors. He designs radiation treatments with pinpoint accuracy, ensuring that tumors get the most effective dose while healthy tissues and organs are spared.
Ann W. Silk, MD, is a medical oncologist who cares for patients with melanoma, and other skin cancers. She also leads clinical trials focused on combination treatment with immunotherapy and viral therapy for melanoma and other cancers.
Drs. Goyal and Silk discuss their work as part of a multidisciplinary team that translates research of investigational treatments and directly applies them to patient therapies.
Managing Multiple Melanoma Brain Metastases
Real World Health Care: How is treatment advancing for patients with multiple brain metastases (MBM) from melanoma?
Sharad Goyal: The treatment of brain metastases from melanoma is controversial and includes surgical resection, stereotactic radiosurgery (SRS) and whole brain radiation (WBRT). Several new classes of agents have revolutionized the treatment of metastatic melanoma, allowing for subsets of patients to have long-term survival. Given this, management of MBM from melanoma is continually evolving.
As patients are living longer due to more effective systemic therapy, surveillance and management of intracranial disease is increasingly important. At this time, the standard of management for patients with MBM from melanoma includes SRS, WBRT, or a combination of both.
In addition, emerging data supports the notion that SRS, in combination with targeted therapies or immune therapy, may reduce the need for whole brain radiation. Prospective studies are required to fully evaluate the efficacy of these novel regimens in combination with radiation therapy. Given the advances in systemic therapy of melanoma, it is critical that oncologists treating these patients be aware of new treatment paradigms to optimize the outcomes for all patients with metastatic melanoma.
RWHC: Are there ways to treat melanoma in order to avoid or lessen the chances of brain metastases? Does early initial detection of melanoma help?
SG: Early detection of melanoma will always help reduce the chance a patient develops brain metastases. There is usually a fairly lengthy period when the tumor expands beneath the top layer of skin but doesn’t go any deeper. This allows time for screening, early detection, treatment, and a full recovery if the tumor is discovered before it spreads.
After a patient is diagnosed with melanoma, the use of certain anticancer treatments that are given after a cancer is surgically removed, such as interferon alfa and ipilimumab, will allow for an improvement in overall survival in patients with stage III or IV melanoma. In addition, the use of anti-PD-1 checkpoint inhibitors prolongs overall survival in patients with stage IV melanoma. Currently, many studies are underway investigating the optimal anticancer treatment in patients with Stage III melanoma.
RWHC: What are the most promising therapies on the horizon for metastatic melanoma?
Ann Silk: Melanoma is the “posterchild” for breakthrough immunotherapies. At Rutgers CINJ, we are testing novel combinations of new agents coupled with immunotherapies. Those novel agents help to “prime” tumors so immunotherapies work better. One example of this is combining an immune checkpoint inhibitor pembrolizumab with intra-tumoral injections of talimogene laherperepvec, which is a live herpesvirus that infects cancer cells, replicates within them, and lyses the cancer cell, thus killing the cell. We’re also seeing promising early results in trials that combine intra-tumoral injections of coxsackievirus with injections of pembrolizumab, with response rate of 60%, which we reported at this year’s American Association of Cancer Research Annual Meeting. We have just recently opened a study in which we will combine IL-2 cytokine therapy with pembrolizumab, a combination of two drugs that have already demonstrated good activity in metastatic melanoma. They are each FDA-approved as single-agents, but we are studying them as a combination therapy. The goal of these studies is to build on the success of immunotherapies to increase response rates, particularly complete response rates.
Access to Clinical Trials
RWHC: What are some of the biggest challenges facing researchers studying metastatic melanoma?
AS: Access to clinical trials is a challenge, from a patient or participant status. Running clinical trials requires vast resources and numerous support personnel, so they tend to be concentrated at large medical centers. As a result, only about five percent of the patient population has access to these trials. I think that number should be closer to 80 percent. Trials aren’t only important for the patients receiving the treatment; the knowledge we gain also helps future patients.
RWHC: What are the biggest challenges facing clinicians treating patients with metastatic melanoma?
SG: One of the most challenging types of cancer to treat is melanoma and the most challenging area it can spread to is the brain. With the advancements being made in cancer treatment, the odds of survival for many of these patients are changing dramatically.
In recent years, our understanding of cancer biology has progressed substantially and this has led to the development of targeted therapies and immunotherapies. These novel therapies have prolonged survival in a disease which previously had a dismal outcome. As patients are living longer due to more effective systemic therapy, surveillance and management of intracranial disease is of increasing importance.
AS: There are many standard therapies approved to treat melanoma, and as indicated earlier, there’s lots of research activity in this area as well. Patients benefit from the wealth of approved therapies on the market. But while about 30-40 percent of patients will respond very well to these therapies, the majority still struggle and succumb to their disease. Patients who don’t respond to the first line of treatment must move on to a second line of treatment. Once those treatment options are exhausted, the only course of action is to try and get the patient enrolled in an investigational therapy trial. In many cases, the patient would benefit from earlier involvement in clinical trials.
Early and Current Inspirations
RWHC: What initially interested you in researching melanoma and treating people with the disease? What continues to inspire you?
AS: I became interested in the interplay between cancer and the immune system in my first job as a data manager at the Dana-Farber Cancer Institute, where I managed one of the first clinical trials of ipilumumab, which was later FDA approved with the distinction of being the first drug that prolonged survival in melanoma. I was inspired by researchers who were on the forefront of personalizing medicine by using the immune system to attack cancer cells. Ever since then, in both my research and clinical practice, I haven’t found any better ally in the fight against cancer than retraining the immune system to attack cancer cells.
SG: Throughout my career, I have been inspired by the cancer patients I treat. The relationships that I have developed with patients and their families are unlike those in almost any other medical specialty. Once a patient has a diagnosis of cancer, I am able to see the patient and his or her family members on a regular basis and develop a long-lasting relationship with them.