New phase 3 study results from the NADINA study suggest that neoadjuvant (neoadj) therapy with ipilimumab (IPI) and nivolumab (NIVO) followed by response-driven adjuvant therapy was associated with increased event-free survival (EFS) in patients with macroscopic stage III melanoma.
The researchers comparing the neoadjuvant IPI+NIVO therapy to the current standard of care (SOC) randomized two groups of patients: one receiving neoadj IPI 80mg + NIVO 240mg every three weeks for two cycles, followed by therapeutic lymph node dissection (TLND) and adjuvant therapy based on pathologic response, and the other group receiving TLND followed by adjuvant NIVO alone. The primary study endpoint was EFS measured from randomization until disease progression, recurrence, or death. A total of 423 patients were enrolled: 212 in the neoadj arm and 211 in the adjuvant arm.
According to the results, the neoadj arm showed a significantly lower number of events when compared to the adj arm (28 vs 72; HR = 0.32; 99.9% CI: 0.15-0.66; p<0.0001). Twelve-month EFS rates were 83.7% in the neoadj arm versus 57.2% in the adj arm. A subgroup analysis showed EFS rates of 83.5% and 52.1% in BRAF-mutant melanoma, and 83.9% and 62.4% in BRAF wild-type melanoma for neoadj versus adjuvant therapy, respectively. A total of 58% of patients achieved a major pathologic response (MPR), 8.0% a partial response (pPR), and 26.4% showed no response (pNR). One-year relapse-free survival (RFS) rates were 95.1% for MPR, 76.1% for pPR, and 57.0% for pNR. Grade ≥3 systemic treatment-related adverse events occurred in 29.7% of the neoadj group and 14.7% of the adjuvant group, with one treatment-related death reported in the adjuvant group.
"Personalized treatment reduces the risks of overtreatment and unwanted side effects. It also helps patients avoid the burden of getting one more year of treatment," said American Society of Clinical Oncology (ASCO) expert Jyoti Patel, MD, FASCO, medical director of thoracic oncology and assistant director for clinical research at the Lurie Cancer Center of Northwestern University, in a press release. "Also, if there were still cancer cells remaining after surgery, adjuvant therapy could be personalized to an appropriate oral medication."
"The results from the NADINA clinical trial show the benefits of giving immunotherapy before surgery for some patients with stage III melanoma where the involved lymph node can be felt,” said ASCO President Lynn Schuchter, director of the Tara Miller Melanoma Center at the University of Pennsylvania, in a press release from the American Cancer Society about the study. “Notably, this treatment approach not only highlights the effectiveness of immunotherapy before surgery but also suggests that we can reduce the overall treatment burden for patients whose melanoma responds to treatment.”
Source: Blank C., et al. J Clin Oncol 42, 2024 (suppl 17; abstr LBA2). Doi:10.1200/JCO.2024.42.17_suppl.LBA2