Melanoma outcomes improved by dual immunotherapy before surgery rather than after
Prof Christian Blank - Netherlands Cancer Institute, Amsterdam, Netherlands
Today I presented the NADINA trial that’s an investigator initiated phase III trial comparing neoadjuvant ipilimumab plus nivolumab versus adjuvant standard of care nivolumab. What we have shown is that already at the first interim analysis with a p-value of 0.0001 we saw a statistically significant benefit for the neoadjuvant therapy with a hazard ratio of 0.32 and an estimated EFS at one year of 83.7% versus 57.2%.
What we also saw is that patients achieving a major pathologic response, that were 59% of the patients, and these patients didn’t receive any adjuvant therapy after the neoadjuvant therapy, that they have a very good outcome. They have an EFS of 95% as compared to patients that had a partial response or non-response that was then only 76% and 57%. That’s still better than the adjuvant arm because the whole cohort on the adjuvant arm had only 57%.
What could be the impact of this research?
In my vision, neoadjuvant ipilimumab/nivolumab is the new standard of care for microscopic stage 3 disease. We have also data from the SWOG-1801 trial where neoadjuvant pembrolizumab was given but then not in a personalised fashion but for all patients adjuvant therapy. This you have to discuss with the patients. The response rates and the EFS is clearly better for the combination but we had also more toxicity – 30% versus 15%. So if a patient is more afraid of the toxicity then you could advise also anti-PD-1 monotherapy neoadjuvant therapy. But if the patient wants to have the combination with the highest response rate and, at the moment, the best event free survival data then they should go for the combination.
In the future we want to personalise that and we have to work also for the patients that are non-responders. Because with an event free survival of 57% this is clearly lower than the 95% that we had in the responders. So here we have to work on novel combinations in the adjuvant part, post neoadjuvant therapy, and hope that we bring this then to at least 80-90%.
