The NADINA trial (NCT04949113) marks a significant milestone in melanoma treatment, representing the first Phase III trial to compare neoadjuvant immunotherapy with the standard adjuvant approach and the first in oncology to assess a neoadjuvant regimen solely comprising immunotherapy. The trial aimed to evaluate whether preoperative treatment with ipilimumab and nivolumab, followed by therapeutic lymph node dissection (TLND) and response-driven adjuvant therapy, offers superior outcomes compared to the current standard of care, which involves adjuvant nivolumab following surgery.1
Between August 2021 and December 2023, 423 patients with stage III melanoma were enrolled and randomized into two groups: 212 patients received the neoadjuvant therapy while 211 patients received the standard adjuvant therapy. The primary endpoint was event-free survival (EFS), defined as the time from randomization until disease progression, recurrence, or death. At the data cutoff on January 12, 2024, with a median follow-up of 9.9 months, there was a notable reduction in events in the neoadjuvant group compared to the adjuvant group (28 vs 72 events, respectively). This translated to a hazard ratio (HR) of 0.32 (99.9% CI 0.15-0.66; p<0.0001).
The estimated 12-month EFS rates were 83.7% for the neoadjuvant arm compared to 57.2% for the adjuvant arm. When stratified by BRAF status, the 12-month EFS rates were 83.5% for BRAF-mutant patients receiving neoadjuvant therapy versus 52.1% for those receiving adjuvant therapy. For BRAF wild-type patients, the rates were 83.9% and 62.4%, respectively. The neoadjuvant approach not only improved EFS significantly but also allowed many patients to avoid further adjuvant therapy if a major pathologic response (MPR) was achieved.2
“What’s important about this trial? It was pure immunotherapy. This is one thing that we need to look at in the whole oncology field. How can we better utilize the immune system using pure checkpoint inhibition or other pure immunotherapies, rather than trying to activate the immune system and then dampening it down with things like chemotherapy?”
In conclusion, the NADINA trial demonstrates the benefits of neoadjuvant immunotherapy for stage III melanoma, providing robust evidence to support its use as a new standard of care. This approach not only improves EFS but also offers a tailored treatment strategy, potentially enhancing patient quality of life by reducing unnecessary exposure to further therapy. The ongoing follow-up and additional data on overall survival will further clarify the long-term benefits of this innovative treatment paradigm.
References:
- Blank, C.U., Lucas, M.W. and Scolyer, R.A. (2024) ‘Neoadjuvant nivolumab plus ipilimumab versus adjuvant nivolumab in macroscopic, resectable stage III melanoma: The phase 3 NADINA trial.’, Journal of Clinical Oncology, 42(17_suppl). doi:10.1200/jco.2024.42.17_suppl.lba2.
- NADINA: Neoadjuvant Ipilimumab Plus Nivolumab Poised to Become a New Standard of Care for Macroscopic Stage III Melanoma. Available at: https://dailynews.ascopubs.org/do/nadina-neoadjuvant-ipilimumab-plus-nivolumab-poised-become-new-standard-care.
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