In 2022, Blank and his research group published the results of the PRADO study, in which 60 out of 99 patients with metastatic melanoma responded well to immunotherapy before surgery. “Conducting these studies eventually led to the design of the NADINA trial, the first phase 3 trial investigating neoadjuvant checkpoint inhibition for early stage melanoma,” Blank states.
In the international investigator initiated NADINA trial, 423 patients were randomized to two groups: the first group received two immunotherapy treatments with ipilimumab and nivolumab, followed by surgery. The second group received standard treatment involving surgery followed by 12 rounds of immunotherapy with nivolumab. “In 59% of patients who had received immunotherapy before surgery, the tumor was nearly entirely or completely gone, which meant that they did not require additional treatment.” Even people who did not respond well to the therapy and had an unfavorable prognosis benefited from the therapy: they were able to start adjuvant treatment with immunotherapy or targeted therapy after surgery.
The effects of the treatment become apparent quickly. After one year, almost 84% of patients who had received neoadjuvant treatment were still tumor-free, compared to 57% of the group receiving standard treatment. Blank: “Patients whose tumors were nearly entirely or completely gone, saw even better results; 95% remained tumor-free, after only six weeks of treatment.” 76% of patients whose tumors were only partially gone were still tumor-free one year after the start of their treatment, compared to 57% of patients who did not respond well to neoadjuvant therapy. These two patient groups received additional adjuvant treatment after their neoadjuvant treatment and surgery. In three years, the researchers expect to know whether this positive trend continues and could improve survivorship. The next challenges in this field will be to improve treatment outcomes of patients who responded less favorably.
Besides a greater chance of tumor-free survival, most patients were able to cut down their treatment time to only six weeks. Blank: “Treatment is a lot cheaper – €16,000 instead of €68,000, which would free up about 30 to 40 million euros in the Netherlands, and could reach a billion euros worldwide.”
The treatment still needs to be registered and approved in the Netherlands to qualify for health care insurance coverage. That’s why it will not be immediately available. Blank: “We are talking with various public authorities to explore the possibilities on receiving coverage of the treatment in the future”
There are many studies looking into neoadjuvant treatments for various cancer types, including lung cancer, bladder cancer, and breast cancer. “These trials often combine a neoadjuvant approach with standard adjuvant treatment after surgery, instead of adapting treatment to the response to the neoadjuvant part,” Blank explains. “The NADINA trial is the very first trial within the oncological field that researched a purely immune-therapeutic and personalized treatment. Eventually we aspire to be able to provide personalized immunotherapy by reading out the tumor RNA in every individual patient, and providing a treatment that we know works best based on the results.”