A single dose of a PD-1 inhibitor prior to surgery for melanoma may put patients in remission, according to a study published in Nature Medicine (Mar. 2019; 25(3):454–461). Immune responses brought on by this therapy can reach their peak as early as seven days after treatment. Researchers reported that this is much earlier than previous studies have shown.
The largest cohort of patients to be treated with anti-PD-1 drugs before surgery, the participants also completed up to one year of anti-PD-1 therapy after melanoma surgery. Those with complete responses after the initial dose have remained cancer-free for more than two years.
“Knowing so much earlier whether or not patients are responding to PD-1 inhibitors may give us the ability to guide them to the most appropriate therapy with the greatest chance for success,” said the lead author Dr. Alexander C. Huang, instructor of hematology-oncology at the University of Pennsylvania Perelman School of Medicine in Philadelphia, in a press release.
A total of 27 patients were treated with one dose of the PD-1 inhibitor pembrolizumab three weeks before undergoing surgery. Eight of the 27 (30%) had a complete response or a major response, with less than 10% of the cancer cells remained at the time of their surgery. All eight patients who responded continued to be free of melanoma at a median follow-up time of 25 months.
“It is amazing that we can have greater confidence early on, based on the way patients respond to this treatment before their cancer is surgically removed, that they will do well,” said co-senior author Dr. Tara C. Mitchell, an assistant professor of hematology-oncology at the University of Pennsylvania.
Furthermore, in their previous investigations, results showed that anti-PD-1 therapy had a peak immune response in the blood around three weeks. This current study illustrated that tumour cells were already eliminated at that point, meaning the immune response itself must have started at an earlier time. Analysis from additional groups of patients confirmed that hypothesis, with immune responses in the blood peaking as early as seven days.
In addition, investigators isolated patterns in how melanoma develops resistance to PD-1 inhibitors after surgery, which may lead to deeper understanding of how to best treat patients in the future. Researchers identified two causes: tumour mutations—such as B2M or TP53—as well as increased activity of cells that naturally suppress the immune system.
“We have now identified patterns in the way the cancer can adapt to survive, meaning we may be able to guess its next move after PD-1 treatment,” said Dr. Huang. “The longer into treatment we go, the more mutations and resistance mechanisms we find, but identifying the means of resistance early after starting therapy in resected tumours means the resistance mechanisms may be more predictable, which is another benefit of giving this treatment before surgery.”