A Single Dose of a PD-1 Inhibitor Before Surgery May Predict Outcomes in Patients With Melanoma
A single dose of a programmed cell death protein 1 (PD-1) inhibitor before resection for melanoma may predict clinical outcomes for patients. Researchers from the Abramson Cancer Center at the University of Pennsylvania—who documented this finding in the largest cohort of patients to be treated with anti–PD-1 drugs before surgery—also showed that immune responses brought on by this therapy can peak as early as 7 days after treatment—much earlier than previous studies have shown. These findings were published by Huang et al in Nature Medicine.
Patients in this study completed up to a year of anti–PD-1 therapy after surgery, and those with complete responses after the initial dose have remained cancer-free for more than 2 years. Further, researchers also identified patterns in the way melanoma that recurs after resection adapts to develop resistance to PD-1 inhibitors, potentially paving the way for greater understanding of how best to help these patients.
“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 study’s lead author Alexander C. Huang, MD, an instructor of Hematology-Oncology in Penn’s Perelman School of Medicine and a Parker Bridge Scholar through the Parker Institute for Cancer Immunotherapy.
Currently, the standard of care in resectable melanoma includes surgery followed by a year of drug treatment in select high-risk patients, which can include immunotherapy like anti–PD-1 treatment.
Study Methods and Findings
Researchers gave 27 patients one dose of the PD-1 inhibitor pembrolizumab 3 weeks before surgery. Eight of the 27 patients (30%) had a complete response or a major response, meaning less than 10% of cancer cells remained at the time of the surgery. All eight patients who responded continue to be disease-free at a median follow-up of 25 months.
The team’s previous studies showed anti–PD-1 therapy had a peak immune response in the blood around 3 weeks, but this analysis showed tumor 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 soon as 7 days.
Researchers also evaluated how tumor cells in patients whose melanoma came back were able to develop resistance to the anti–PD-1 therapy. The study identified two causes: tumor mutations, such as B2M or TP53; as well increased activity of cells that naturally suppress the immune system.
“We’ve now identified patterns in the way the cancer can adapt to survive, meaning we may be able to guess it’s next move after PD-1 treatment,” Dr. Huang said. “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 tumors means the resistance mechanisms may be more predictable, which is another benefit of giving this treatment before surgery.”
Researchers said future studies will focus on altering postsurgical therapies based on presurgical responses.
Disclosure: This study was supported by the Specialized Program of Research Excellence (SPORE) in Skin Cancer, a National Cancer Institute Cancer Center Support Grant, the National Institutes of Health, the Tara Miller Foundation, the Melanoma Research Alliance, the David and Hallee Adelman Immunotherapy Research Fund, the Heisenberg program, The Parker Institute for Cancer Immunotherapy Bridge Scholar Award, and Merck, Inc. The study authors' full disclosures can be found at nature.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
