For patients with metastatic melanoma, administering immunotherapy before surgery has shown to be remarkably effective. In fact, in 59% of patients, this approach is so successful that additional post-surgery treatment isn't necessary. These results come from the newly published NADINA study.

Led by experts from the Netherlands Cancer Institute, the NADINA trial has been recognized as one of the top eleven clinical studies projected to greatly impact healthcare in 2024, as stipulated by Nature Medicine. Today, medical oncologist and head researcher Christian Blank shared the promising results at ASCO 2024, the American Society of Clinical Oncology's annual conference in Chicago. The findings have also appeared in the New England Journal of Medicine (NEJM).

The journey leading up to NADINA
The conventional treatment for stage III metastatic melanoma has typically involved surgical removal of affected lymph nodes, followed by a year of immunotherapy or targeted therapy. "Unfortunately, within 3 to 5 years, roughly half of such patients see the disease return," explained Blank. A decade ago, this realization prompted him to create the OpACIN trial, which compared pre-surgery (neoadjuvant) immunotherapy with post-surgery (adjuvant) immunotherapy. Neoadjuvant therapy triggered a more potent immune response, albeit with increased side effects. In order to optimize it, Blank then launched the OpACIN-neo trial, where dosing schedules were tested and refined. The PRADO trial followed, using this optimized dosage on 99 patients, some of whom were able to avoid both surgery and post-surgery treatment.

By 2022, Blank’s team demonstrated through PRADO that 60 out of those 99 metastatic melanoma patients responded well enough to pre-surgery immunotherapy to skip surgery. "Building on this progress, we crafted NADINA, the first phase 3 trial to explore checkpoint inhibitors in early-stage melanoma before surgery," Blank added.

Impressive response rates
In the NADINA study, 423 patients were randomly assigned to two groups: the first received two rounds of immunotherapy using ipilimumab and nivolumab before undergoing surgery. The second group underwent surgery first, followed by 12 immunotherapy sessions with nivolumab. For those receiving immunotherapy before surgery, 59% saw their tumors nearly or completely vanish, meaning they no longer required further treatment. Even individuals with poor responses still experienced some benefit, enabling them to start post-surgery treatments.

Benefits multiply
The effects were observed rapidly. After just one year, nearly 84% of patients treated pre-surgery remained tumor-free, compared to 57% on the standard pathway. Blank elaborated, "For patients whose tumors disappeared almost completely, the numbers were even more striking—95% were disease-free just six months in." For patients with partial tumor reduction, 76% remained tumor-free after one year, while only 57% of those with minimal response did so. Those in the latter group went on to receive additional post-surgery care. In the next three years, researchers will observe whether this trend continues, aiming to improve outcomes for patients who respond less favorably.

In addition to better survival chances, many patients reduced their overall treatment time to just six weeks. Blank remarked, "This approach cuts costs significantly—from €68,000 to €16,000—potentially saving 30 to 40 million euros nationwide and up to one billion euros globally."

However, the therapy has yet to be officially approved and incorporated into the Dutch healthcare system. "We're collaborating with regulators to expedite insurance coverage for this treatment," Blank assured.

Personalizing treatments for the future
Many studies are currently underway to test neoadjuvant immunotherapy for other cancers, such as lung, bladder, and breast cancer. However, as Blank pointed out, these trials usually combine the neoadjuvant approach with post-surgery treatments, rather than adapting to how patients respond to the pre-surgery phase. "NADINA is unique in being the first major cancer trial to explore immunotherapy alone in a highly personalized manner. Our ultimate goal is to tailor treatment based on individual patients’ tumor RNA, ensuring that patients receive the most effective care for their unique situation," he concluded.

Journal

New England Journal of Medicine

Method of Research

Randomized controlled/clinical trial

Subject of Research

People

Article Title

Neoadjuvant nivolumab and ipilimumab in resectable stage III melanoma

Article Publication Date

2-Jun-2024