International consortium publishes recommendations for neoadjuvant
Clayton R. Boldt, Ph.D.
An international consortium, led in part by clinicians and researchers from The University of Texas MD Anderson Cancer Center, has published a series of best-practice recommendations for conducting clinical trials for neoadjuvant, or pre-surgical, therapies in patients with locally advanced melanoma.
The report, published in Lancet Oncology, provides recommendations for clinical trial design, including patient inclusion criteria, treatment duration, statistical endpoints, surgical considerations, and biospecimen collection and analysis. These guidelines are intended to align the field with standard practices that will maximize the impact of neoadjuvant trials through pooling study of data and more rapidly bring effective therapies to patients with earlier stage disease.
Systemic neoadjuvant therapy has proven effective for several cancer types and is increasingly common as a treatment approach. However, melanoma treatment before surgery has not been widely studied because it is only recently that effective treatment options have emerged.
New targeted and immune therapies have proven effective at treating patients with stage IV, or metastatic, melanoma, so clinicians would like to test these agents in those with earlier stage disease, explained Rodabe Amaria, M.D., assistant professor of Melanoma Medical Oncology and co-first author of the paper.
New drugs have revolutionized treatment
“Current approaches have proven inferior for our patients with locally advanced disease, so there is a lot of interest in trying to move these new therapies into earlier stages to hopefully improve the chance of curing these patients,” says Amaria. “The challenge is this is a relatively small patient population, and so we needed to organize ourselves as a field to create the most high-impact trials that will help us learn as much as possible.”
The American Cancer Society estimates 96,480 melanomas will be diagnosed in the United States this year, and just about 15 percent of those will have stage III, or locally advanced disease.
Based on that population size, it would be hard for any single neoadjuvant therapy trial to generate data sufficient to obtain approval by the U.S. Food & Drug Administration (FDA), according to Elizabeth Burton, director of melanoma research planning & development in Surgical Oncology and co-first author.
“Most studies being conducted in the neoadjuvant setting are single-center trials, and they all were done a bit differently,” says Burton. “When talking with colleagues in other fields and experts from the FDA, we realized that there was no established path for moving therapies into earlier stages for patients with melanoma.”
Getting beyond single-center clinical trials
Thus, there was a desire to convene a group of experts in the melanoma field to establish best-practices for conducting these trials. Experts from MD Anderson, the Melanoma Institute of Australia and the Netherlands Cancer Institute therefore came together to establish the International Neoadjuvant Melanoma Consortium (INMC) in 2016.
The INMC incorporates experts from many disciplines, including experts in medical oncology, surgical oncology, pathology, translational research, statistics and radiology. The earliest meetings also included breast cancer experts, who are well-versed in the field of neoadjuvant treatment, and the FDA, who provided insight into what would be needed for regulatory approval.
Since its inception, the INMC has grown to more than 220 members around the world. The group meets at least annually, with satellite meetings often focusing on specific areas or disciplines.
“We’ve seen that there’s a lot of interest in neoadjuvant melanoma trials, both from physicians as well as pharmaceutical companies,” says Amaria. “There was a lot of buy-in from the start, and the support and enthusiasm been steadily increasing with each meeting we have.”
Many of those from MD Anderson also are part of the Melanoma Moon Shot® team, a group driven to save the lives of patients by advancing novel prevention, early detection and personalized therapeutic strategies. Several neoadjuvant trials at MD Anderson have been sponsored by the Moon Shots Program®, as well as some of the first INMC meetings.
Going forward, the INMC will continue to work collaboratively to advance novel trials designed around these best-practices. Having standard approaches will allow physicians and researchers around the world to pool data from multiple trials to learn about the most effective treatments and more easily apply for regulatory approval of neoadjuvant therapies with the FDA.