Opdivo (nivolumab) + Yervoy (ipilimumab) Before Surgery in Resectable Stage III Melanoma. What the NADINA Trial Showed
The New England Journal of Medicine has published the results of the phase III NADINA trial in patients with resectable stage III melanoma. The trial compared neoadjuvant Opdivo (nivolumab) + Yervoy (ipilimumab) followed by surgery against surgery followed by adjuvant nivolumab. The neoadjuvant approach delivered a marked benefit in event-free survival.
In brief: what happened
423 patients were randomized in the trial. The 12-month event-free survival was 83.7% in the neoadjuvant group and 57.2% in the adjuvant group. The risk of progression, recurrence or death was reduced by 68% (HR 0.32; p<0.001). Grade 3 or higher adverse events related to systemic treatment were observed in 29.7% of patients in the neoadjuvant group and in 14.7% in the adjuvant group.
Why this matters in practice
NADINA confirms the hypothesis that in resectable stage III melanoma systemic treatment can and should be discussed already before surgery. For practice this means a shift from surgery as the first step to a model in which the decision about neoadjuvant immunotherapy becomes part of the starting strategy.
Limitations / what does not change yet
This concerns resectable macroscopic stage III melanoma. These data do not apply to early stages, and they do not apply to unresectable or widely metastatic disease. The toxicity of the combination is higher than with nivolumab alone, so the decision requires careful patient selection.
When a second opinion is especially useful
- you are offered surgery right away without any discussion of systemic therapy;
- doctors' opinions differ on the sequence of treatment;
- resectability and the risk of toxicity need to be assessed;
- it is important to understand whether dual immunotherapy is right for you.
What to prepare for the consultation
- histopathology report;
- PET-CT or CT, if performed;
- brain MRI, if performed;
- a description of the involved lymph nodes or soft-tissue lesions;
- BRAF status data, if the test has already been done;
- list of comorbidities and medications.
Frequently Asked Questions
Does this treatment cancel surgery?
No. In NADINA, surgery remained a mandatory part of the treatment route.
Is this regimen suitable for all patients with melanoma?
No. Only for patients with resectable macroscopic stage III melanoma.
Is toxicity higher than with nivolumab monotherapy?
Yes. The rate of severe systemic adverse events was higher in the neoadjuvant group.
More answers on the FAQ page.