New research by scientists at the University of Texas MD Anderson Cancer Center in Houston has revealed that patients with late-stage melanoma, who were treated with a novel combination of immunotherapy drugs before surgery, had a greater chance of survival four years later. Moreover, the researchers identified biomarkers that could help predict a patient’s response to the combination therapy.
Currently, the standard of care for stage III melanoma involves the surgical removal of the primary tumor and sometimes the dissection of the lymph nodes, followed by adjuvant cancer therapy, such as chemotherapy or immunotherapy. The five-year survival rate for people with stage III melanoma varies between 32% and 93%.
However, stage III melanoma still has a high risk of recurring despite surgery. Therefore, to increase survival rates for melanoma patients, researchers and physicians are increasingly looking at neoadjuvant immunotherapy approaches. This means that the patient undergoes immunotherapy treatment before having the surgery to remove the cancer.
In the latest study, published in the Journal of Clinical Oncology and titled “Long-Term Survival and Biomarker Analysis Evaluating Neoadjuvant Plus Adjuvant Relatlimab (anti-LAG3) and Nivolumab (anti-PD1) in Patients With Resectable Melanoma,” the researchers analyzed the data of 30 Phase II clinical trial patients who had received a combination therapy of the immune checkpoint inhibitors nivolumab and relatlimab before the surgical removal of the primary tumor and after the surgery.
Four years after the neoadjuvant treatment with this combination therapy, 87% of stage III melanoma patients were alive, and 80% of patients were disease-free. Those patients who showed a significant, pathologic response to the treatment at the time of surgery had an even higher recurrence-free rate of 95%.
“If immunotherapy eliminates most of the tumor before surgery, then we have sufficiently trained the immune system for an antitumor response, which minimizes the possibility of recurrence,” explained corresponding author Elizabeth Burton, PhD, and executive director of MD Anderson’s Strategic Research Initiative Development program.
“We are encouraged by these results showing the long-term benefit of this combination and approach for our patients and the opportunity it provides to learn as much as possible about what is driving this response to treatment.”
Following these positive results, the researchers wanted to see if they could find certain biomarkers that might help with identifying patients who respond well or not so well to the combination therapy.
The team discovered that patients who had high levels of a biomarker called TIGIT before the treatment and low levels of the biomarker B7-H3 had the greatest chance of having a significant pathologic response and remaining recurrence-free. High levels of B7-H3, on the other hand, were associated with resistance to the treatment and a greater chance of cancer recurrence.
“[…] The neoadjuvant treatment approach allows us to quickly evaluate the clinical impact of a treatment and serves as a springboard for biomarker research,” explained Burton. “This is a good starting point for where researchers can look in terms of mechanisms of resistance that could be potential therapeutic targets in the future.”
The team is now collaborating with researchers at the James P. Allison Institute at the MD Anderson Cancer Center to validate the biomarkers, to understand their location, and how they influence the tumor microenvironment.
The clinical trial was funded by Bristol-Myers Squibb.
