A follow-up report with data from NADINA was presented at the European Society for Medical Oncology (ESMO) Congress on September 14, 2024. As the primary endpoints already demonstrated benefit1, the updates to this data and the secondary endpoints were highlighted.2

NADINA is a phase 3 trial that enrolled 423 patients between 2021 and 2023 with resectable, macroscopic Stage III melanoma. There are two treatment arms; the first arm has two cycles of neoadjuvant (or up-front; before surgery) ipilimumab plus nivolumab followed by surgery (n=212) against another treatment arm with surgery first followed by 12 cycles of adjuvant nivolumab (n=211).

Results demonstrated that neoadjuvant ipilimumab plus nivolumab followed by surgery resulted in longer event-free survival (83.7% at 12 months) than surgery followed by adjuvant nivolumab (57.2% at 12 months).1

These results, announced earlier this year, were significant and unveiled a new and better standard of care for patients with Stage III melanoma.3 Prior to NADINA, medical intervention started with surgery, and was followed with drug therapy for most types of cancer, including melanoma. Rarely would drug therapy be initiated before surgery before these results.

The updated data presented at ESMO is consistent with previous reports showing the survival benefit for the neoadjuvant arm. The event-free survival of the neoadjuvant treatment arm (80.8% at 18 months) remains significant compared with the adjuvant treatment arm (53.9% at 18 months). Both Stage IIIB and Stage IIIC melanoma show better recurrence-free survival and distant metastasis-free survival with neoadjuvant therapy.2

The distant metastasis-free survival of the neoadjuvant treatment arm (85.7% at 18 months) remains significant compared with the adjuvant treatment arm (62.4% at 18 months). When metastasis appeared, more tumors were found in the adjuvant arm in the bone (n=4 neoadj. vs n=14 adjuvant), liver (n=8 neoadj. vs n=17 adjuvant), lungs (n=9 neoadj. vs n=19 adjuvant), or distant lymph nodes (n=5 neoadj. vs n=13 adjuvant). Brain was relatively similar (n=8 neoadj. vs n=6 adjuvant) for first distant metastasis.2

Based on the follow-up results, the impact of NADINA remains consistent with previous reports. The standard of care for Stage III melanoma has changed based on this clinical trial.

References

1. Blank CU, Lucas MW, Scolyer RA et al. Neoadjuvant Nivolumab and Ipilimumab in Resectable Stage III Melanoma. N Engl J Med. 2024 Jun 2. doi: 10.1056/NEJMoa2402604.

2. Lucas MW, Menzies AM, Lopez-Yurda RA et al. Distant metastasis-free survival of neoadjuvant nivolumab plus ipilimumab versus adjuvant nivolumab in resectable, macroscopic stage III melanoma: the NADINA trial. EMSO Congress. September 14, 2024.

3. O’Leary K. Neoadjuvant immunotherapy a new standard of care for melanoma. Nat Med. 2024 Jun 17. doi: 10.1038/d41591-024-00045-x.