S1801 was a randomised phase II trial. Participants were randomised 1:1 to either adjuvant therapy or neoadjuvant therapy. It was patients with stage 3b to stage 4 resectable melanoma and these participants on the adjuvant arm received surgery followed by 18 doses of flat dose pembrolizumab. On the neoadjuvant arm they got three doses of pembrolizumab, then surgery and then 15 doses. The only thing we changed between the two arms was the sequence; both arms got the same surgery and the same number of pembrolizumab doses.

What we found at a median of 14.7 months of follow-up is that the event free survival was significantly better in the patients who received pembrolizumab in the neoadjuvant regimen rather than entirely after surgery. So the implications mean that just by simply changing the sequence of when you give immunotherapy for an immune responsive cancer, leaving the cancer in place for a short period of time, giving drug first, will expand a bigger population of T-cells to give you a more prolonged immune response and a longer benefit.

In the future we plan to collect the samples and clarify the pathologic response – how well did the medicine or the T-cells kill tumour and do those variable responses in pathologic response correlate to outcomes?  

At 14.7 months there were only 36 events for survival. This was a 345 patient study, so really it’s underpowered for overall survival at this look. We’ll be reporting that probably in the longer term but at this point in time S1801 is practice changing for melanoma patients around the world. If you have resectable melanoma instead of going straight to surgery you should get some immunotherapy first and then go to surgery.